Effects of Cannabis Use in Cancer Patients: A Feasibility Study
Conditions: Solid Tumor, Adult
Sponsor: University of Colorado, Denver

 
 
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Effects of Cannabis Use in Cancer Patients: A 
Feasibility Study 
 
Protocol Number: 
 
18-0836 
Principal Investigator:
 
Angela Bryan, PhD 
Co-Investigators: 
Ross Camidge, MD, PhD; Daniel Bowles, MD; 
Cinnamon Bidwell, PhD; Jost Klawitter, PhD 
Coordinating Center:  
University of Colorado Boulder 
 
 
Version Date: 
 
ClinicalTrials.gov ID:  
May 31st, 2022 
 
NCT03617692 
 
 

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STATEMENT OF COMPLIANCE 
 
This is an investigator-initiated study. The principal investigator Angela Bryan, PhD, is conducting 
the study and acting as the sponsor. As the sponsor-investigator, both the legal/ethical obligations 
of a PI and those of a sponsor will be followed. 
 
The trial will be carried out in accordance with Good Clinical Practice (GCP) as required by 
applicable United States (US) laws and applications, including but not limited to United States 
(US) Code of Federal Regulations (CFR) as applicable (45 CFR Part 46, 21 CFR).  
 
 
The PI will assure that no changes to the protocol will take place without documented approval 
from the Institutional Review Board (IRB). All personnel involved in the conduct of this study 
have completed Human Subjects Protection Training.  
 
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments.  
 
 
 
Principal Investigator  
Print/Type Name:  
 
 
Signed:   
 
 
 
 
 
 
 
 
 
Date:   
 
  
 
 

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LIST OF ABBREVIATIONS 
 
ACRONYM 
DESCRIPTION 
11-OH-THC 
11-Hydroxy-Δ⁹-tetrahydrocannabinol 
AUDIT 
Alcohol Use Disorder Identification Test 
BAI 
Beck Anxiety Inventory 
CAT 
Computerized Adaptive Test 
CBC 
Cannabichromene 
CBD 
Cannabidiol 
CBD-A 
Cannabidiolic Acid 
CBG 
Cannabigerol 
CBG-V 
Cannabigevarin 
CBN-COOH 
Carboxy- cannabinol 
CI 
Confidence Interval 
Co-I 
Co-Investigator 
EMR 
Electronic Medical Record 
FACT-Cog 
Functional Assessment of Cancer Therapy - Cognitive 
FACT-G 
Functional Assessment of Cancer Therapy - General 
FDA 
Food and Drug Administration 
IIT 
Investigator-Initiated Trial 
HPLC-MS 
Multianalyte high-performance liquid chromatography + tandem mass 
spectrometry 
M 
mean 
MCQ 
Marijuana Craving Questionnaire 
Mg 
milligram 
N 
Number of participants 
NIDA 
National Institute on Drug Abuse 
NIH 
National Institutes of Health 
OCRST 
Oncology Clinical Research Support Team 
OR 
Odds Ratio 
PI 
Principle Investigator 
PSQI 
Pittsburgh Sleep Quality Index 
REDCap 
Research Electronic Data Capture 
STAI 
State-Trait Anxiety Inventory 
THC 
Δ⁹-tetrahydrocannabinol 
THC-COOH 
Carboxy- Δ⁹-tetrahydrocannabinol 
THC-V-COOH 
Carboxy- Δ9-tetrahydrocannabivarin 
TLFB 
Timeline Followback Substance Use Assessment 
UCH 
University of Colorado Hospital 
VA 
Veterans Affairs Medical Center 
 
 

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PROTOCOL SUMMARY / SYNOPSIS 
Protocol Title: 
Effects of Cannabis Use in Cancer Patients: A Feasibility Study 
 
Objectives: 
 
• Primary Objective: 
The goal of this study is to determine the feasibility of a human 
observational study of orally administered Cannabis use among 
cancer patients, towards developing feasibility/pilot data in support 
of an R01 grant application to the National Cancer Institute. The 
primary objective will be to enroll 30 patients and demonstrate 
reasonable compliance with study procedures within fifty-four 
months of active recruiting.  
 
 
Endpoint: 
• Recruitment Outcomes: 
Number of interested patients who contact the research team  
Number of eligible potential participants 
Number of enrolled eligible participants 
Number of study assessments completed by enrolled participants 
Number of participants who complete the study 
 
Population: 
• Sample size 
o Maximum number of participants that can be enrolled is 
150 (allow for screen failures)  
o Minimum number of participants to be enrolled: 30 
(number of participants needed to answer scientific 
question/aims) 
• Gender 
o Male and Female 
• Age Range  
o 21-100 
• Demographic group  
o Have a diagnosis of any solid tumor type who has or is 
undergoing either curative or palliative treatment 
• General health status  
o Oncology Patients 
• Geographic location  
o Denver/Boulder Area 
 
Phase: 
Pilot 
Number of 
Participating Sites 
enrolling 
participants: 
UC Central; UC Boulder 

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Description of Study 
Agent: 
Self-Administered Cannabis 
Study Duration: 
Fifty-Four Months 
 
 
 
 
 

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SCHEMATIC OF STUDY DESIGN 
 
 
1 
PARTICIPATING SITES 
A complete and current listing of investigators, research personnel, research facilities and other 
study centers (if applicable) participating in this study will be maintained throughout the duration 
of this study on a Protocol Contact List form, incorporated herein by reference.  
 
2  
INTRODUCTION: BACKGROUND INFORMATION AND 
SCIENTIFIC RATIONALE                   
2.1 
BACKGROUND INFORMATION  
2.1.1. Cannabis Use and Cancer. The American Cancer Society (www.cancer.org) quotes a 
lifetime risk of invasive cancer of 42% in men and 38% in women in the USA. Consequently, 
with the emergence of medical Cannabis as a therapeutic option in many states, particularly for 
cancer treatment-related symptomatology, this population represents one of the largest 
opportunities for real world medical Cannabis use research. As of early 2017, twenty-nine states 

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and the District of Columbia have legalized medical Cannabis programs. Importantly, 
recreational use is now legal in several states, making Cannabis even more accessible to 
potential medical users even without a doctor’s explicit recommendation or prescription. Recent 
polls indicate that 77% of Americans believe that Cannabis has legitimate medical purposes2. 
Likewise, a recent poll of physicians in North America found that 76% would recommend the 
use of Cannabis to alleviate symptoms, specifically in the case of a patient suffering from 
advanced cancer and severe cancer treatment-related side effects3. In addition, because of its 
potential to target multiple symptoms, it has been suggested that Cannabis might reduce 
polypharmacy among cancer patients4. While there is a great deal of cultural support for medical 
Cannabis programs, cancer patients and doctors alike have very little scientific information on 
which to base decisions regarding whether or not to use Cannabis or which product, cannabinoid 
composition, or route of administration to use5. This information is critical as some products may 
be more or less beneficial, or more or less harmful in this population. Given the fact that 
acceptance of and access to Cannabis is rapidly increasing across the nation, research on 
the risks and benefits of legal market cannabis use in this vulnerable population should 
clearly be a high priority. The bulk of research on the use of medical Cannabis in cancer 
focuses on physical symptom reduction, while in contrast almost no studies have examined the 
psychological and cognitive impacts of medical Cannabis on cancer patients. This lack of 
research is surprising, given that the importance of examining new strategies with the potential to 
improve quality of life in cancer care is well-recognized among clinicians6. 
As noted, research examining medical Cannabis use in cancer patients has focused primarily 
on the effects of Cannabis on the reduction of physical symptoms related to cancer and anti-
cancer treatment (e.g., chemotherapy). Recent reviews of this literature suggest that there is some 
evidence that medical Cannabis and/or synthetic cannabinoids can alleviate nausea and 
vomiting, stimulate appetite, reduce pain, alleviate anxiety, and mitigate neuropathy in this 
population7,8. Importantly, some studies have illustrated that Cannabis may be more effective 
and/or desirable than standard treatments for these symptoms. For example, a review of 30 
randomized studies investigating antiemetic properties of Cannabis compared to either placebo 
or standard antiemetics found that oral cannabinoids were more effective at reducing nausea and 
vomiting, and in these studies, between 38 and 90% of patients reported that they preferred the 
cannabinoids9. While its antiemetic properties are clear, much less is known about other potential 
beneficial effects. 
The current state of the research on Cannabis is fraught with important limitations. Most 
relevant to the current proposal is the fact that much of the research on cannabinoids in cancer 
treatment examines the effects of synthetic cannabinoids administered in capsule form (e.g., 
nabilone, dronabinol10). However, given the changing legal status and availability of Cannabis 
both recreationally and medicinally, it is increasingly the case that cancer patients who use 
Cannabis are using it in plant derived form. While there are a vast number of products available 
in state-regulated medical and recreational markets, there is very limited research on how these 
new products might influence the consumer. Cannabis in its plant form contains more than 60 
different cannabinoids, and the potencies of each vary significantly across strains10,11. One of 
these cannabinoids, cannabidiol (CBD) may actually mitigate detrimental psychological effects 
of the more well-known and psychoactive cannabinoid, ∆9-tetrahydrocannabinol (THC)12. Yet 
most published research on Cannabis in cancer care equates effects of isolated synthetic THC to 
the far more complex plant form. The current proposal seeks to assess the feasibility of 
conducting a fully-powered study of the effects of plant-derived legal market Cannabis as used 

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by current cancer patients. Specifically, we wish to determine whether it is feasible to appraise 
the effects of orally administered Cannabis products among a cancer patient group by 
determining whether this group is willing to participate in all necessary components of a study 
examining   how differing ratios of cannabinoids in cannabis products (based on type of product 
strain used) relate to symptom relief, quality of life, and cognitive measures. 
2.1.2. Psychological effects of Cannabis use in cancer patients. There is some research that 
suggests the potential for positive psychological effects of Cannabis use that may improve 
quality of life. For example, some of the effects that are commonly described as adverse or 
harmful (e.g., feeling “high”, euphoria, sleepiness), may be reframed as positive effects for those 
suffering from cancer and the side effects of treatment (i.e., mood elevation, reduced anxiety, 
improved sleep quality)7. One study examined the effects of medical Cannabis on psychological 
symptom management by interviewing Israeli cancer patients before and 6-8 weeks after they 
received a medical Cannabis license, and found reductions in self-reported mood disorders, sleep 
disorders, and pain, as well as reduced use of pain medication and depression/anxiety medication 
after initiation of medical Cannabis use. Given these findings, the study authors concluded that 
medical Cannabis may be an important contribution to palliative cancer care13.  
At the same time, it is important to acknowledge the potential negative effects. Specifically, 
the literature is fairly clear that acute use of Cannabis temporarily compromises cognitive 
function. For example, one study observed impaired performance on an executive function task 
and two motor control tasks after a 13% THC dose of Cannabis13. On the other hand, the 
evidence is mixed regarding the long-term effects14,15. Notably, this evidence base is somewhat 
limited in that relatively few researchers have examined these effects, and results of such studies 
have in some cases been inconclusive or have important limitations (including studying only the 
effects of very low doses of THC that are rarely used in the real world)15. Regardless, it is nearly 
inevitable that cancer patients are faced with both self-regulatory challenges (i.e., adhering to 
complicated drug regimens, healthy eating, exercising to reduce fatigue) as well as cognitively 
taxing decisions (e.g., weighing pros and cons of treatment options) that rely on high-level 
working memory and executive function processes that may be influenced acutely by Cannabis 
use. Further, one of the greatest concerns of cancer patients and survivors are changes to their 
cognitive abilities16–18. Research using traditional neuropsychological assessment has 
documented deficits in processing speed, attention/working memory and episodic memory19–21. 
Moreover, cancer patients’ subjective reports of cognitive difficulties are often greater than the 
deficits when compared to performance on objective tests22. Finally, there is a large body of 
research demonstrating that cancer patients may experience reduced cognitive functioning due to 
the effects of chemotherapy23. Thus, it is essential to examine the impact of Cannabis use on 
both objective and subjective cognitive function in this already-vulnerable population. 
2.1.3. Synergistic effects of multiple cannabinoids on pain, anxiety, and insomnia. It is worth 
noting that pain, anxiety, and insomnia are three of the most common complaints among cancer 
patients and are also the three most common conditions cited for use of medical Cannabis24. 
Importantly, an expert panel convened by the National Academies of Sciences, Engineering, and 
Medicine concluded in their 2017 report that there was conclusive evidence that Cannabis is 
effective for treatment of chronic pain, moderate evidence for its effect on sleep outcomes, and 
limited evidence for effects on anxiety25. They also concluded that there is conclusive evidence 
for Cannabis effectiveness at treating chemotherapy-induced nausea and vomiting, however this 
was the only symptom domain where research has been conducted primarily or exclusively with 

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cancer patients. Further, much of the existing research has been conducted with synthetic 
individual cannabinoids. Thus, research on pain, insomnia, and anxiety among cancer patients 
and using products widely available in the legal market is critically needed. Currently, relief 
from chronic pain is by far the most common condition cited by patients for use of medical 
Cannabis in U.S. states with legal markets; 87%-94% of self-reported medical Cannabis users 
report using Cannabis for relief of a pain condition26,27. Treatment of anxiety and insomnia are 
the next most common medical uses24. In addition, there is some evidence that individuals are 
replacing the use of traditional pain, mood, and sleep medications with Cannabis. For example, 
one recent study reported survey data suggesting that medical Cannabis use in pain patients was 
associated with a 64% decrease in opiate use28. A second study recently observed significantly 
lower opiate overdose deaths in states with medical access to Cannabis29. Similarly, recent 
analyses of prescription data in states with medical access to Cannabis suggest a significant 
reduction in the prescription of medications for pain, anxiety, and sleep dysfunction30.  
Pain. Across five high quality reviews conducted in the past four years, results were 
consistent in suggesting that cannabinoids demonstrate an effect on pain31–35. For example a 
rigorous, systematic review by Whiting et al35 covered 28 chronic pain studies (2454 
participants) primarily conducted in Canada or Europe. Twenty-two of these studies evaluated 
plant-derived cannabinoids (cannabis extract mouth spray or nabiximols n=13, plant flower that 
was smoked or vaporized n=5, oramucosal spray n=3, oral THC n=1) while 5 studies evaluated 
synthetic THC (i.e., nabilone). All of the selected studies included either an active comparator or 
placebo control. Analyses across studies that evaluated the effects of inhaled plant-derived 
Cannabis suggested a statistically significant effect on the odds of a 30% or greater improvement 
in pain (OR = 1.41). The largest single effect size presented across the reviews was observed 
with inhaled Cannabis on pain [e.g. OR, 3.43; 38]. Consistent with this, an average OR of 3.22 
(CI: 1.59 to 7.24) was found across 9 doses of inhaled THC tested across five studies31. While 
the analgesic properties of THC are the most widely studied, pharmacological and clinical data 
suggest that cannabidiol (CBD) is another primary cannabinoid that may work synergistically 
with THC in a multi-target analgesic approach to pain relief. For example, nabiximols which are 
an administration of a plant-based mixture of THC and cannabidiol (CBD) via mouth or nasal 
spray were associated with significant reductions in numerical pain ratings across the available 
studies. 
Anxiety/affect. There is evidence demonstrating that Cannabis use is associated with 
increased anxiety and anxiety disorders36. However, other data, including our own prospective 
work, suggests that Cannabis use may be protective for anxiety and may decrease the chances of 
developing an anxiety disorder37. A number of studies have found that Cannabis acutely 
increases positive mood and measures of reward38,39 even when using a “balanced placebo” 
design to control for expectancy effects40. This finding is consistent with a growing body of 
evidence from animal models suggesting that Cannabis has anxiolytic effects41. Overall, 
however, research studies have largely ignored the fact that Cannabis exists in different forms 
with differing ratios of THC to CBD and have not characterized the effects of Cannabis as the 
compound action of different cannabinoids that vary in terms of their pharmacological effects. 
Two primary cannabinoids, THC and CBD, may have opposing effects with regard to anxiety. 
Importantly, THC is thought to be acutely anxiogenic42, while treatment with CBD has 
anxiolytic effects without the experience of a “high”43. Clarifying the anxiolytic effects of 
specific strains that differ in their cannabinoid composition may explain these discrepant 
findings.  

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Sleep. THC has been shown to dose dependently reduce wake time and increase Stage 4 
sleep across human and animal studies44,45. Whereas it has been well established that THC 
promotes sleep, contradictory results on the effect of CBD on sleep have been reported. For 
instance, an early study found a diminution in sleep after systemic administration of CBD46, 
whereas other work showed an improvement in sleep in insomniacs after using CBD47. Much of 
this work has been done, again, with synthetic oral forms of THC and CBD in isolation, leaving 
a limited knowledge base on the effects of the synergistic effects of plant-derived cannabinoids 
in common forms of administration.  
A 2017 survey study of cannabis use among cancer patients showed that pain, stress, and 
sleep were all identified as reasons for Cannabis use5. Though the study did not ask specifically 
about quality of life, over half (51%) of patients felt that Cannabis was a “major benefit” while 
another 39% agreed it was a “moderate benefit.” It is logical to assume, therefore, that to the 
extent that Cannabis alleviates negative symptoms from cancer and cancer-treatment, it should 
also increase overall quality of life. Also, while there is evidence to suggest that Cannabis may 
be effective for pain, anxiety, and sleep—and consequently quality of life—it is not clear 
whether these effects are driven by one of the primary cannabinoids (THC or CBD) or the 
synergistic combination of the two. Overall, very little is known about the efficacy, dose, routes 
of administration, or side effects of commonly used Cannabis products in the U.S that come in a 
variety of potencies and cannabinoid contents, nor critically how these products may work 
differently in cancer patients.  
2.1.4. THC and cognitive impairment. A number of studies indicate that Cannabis produces 
acute cognitive impairment, especially relating to memory and attention during intoxication and 
possibly for hours to days after use48,49. For example, studies that were published as early as the 
1970’s suggest that Cannabis disrupts immediate and delayed free recall of information e.g., 50,51. 
Recall of words from a list is one of the most common approaches to demonstrating the effect of 
THC on recall performance e.g., 52. Studies have also suggested working memory may be the most 
sensitive to the acute effects of Cannabis see 53. Among the studies that included two THC 
concentrations, higher doses mostly yielded greater cognitive impairment15,54–56. In 
neuroimaging work, Cannabis users showed differential brain response to an associative memory 
task while under the influence of THC compared with a placebo. Specifically, THC attenuated 
brain activity in the insula, right inferior frontal gyrus (IFG) and left middle occipitals gyrus 
during encoding, and increased network-wide activity during recall. Taken together, these results 
suggest that THC has a negative effect on the neurocognitive processes involved with encoding, 
and neural activation changes during recall likely reflect a compensatory mechanism for the 
affected encoding. That is, the memory system as a whole must work harder in order to account 
for the cognitive deficits induced by THC. In sum, the literature suggests that acute 
administration of Cannabis impairs the encoding and retrieval of information, albeit to a modest 
degree, and these effects may be dose-dependent on THC level. Further, this Cannabis-induced 
cognitive impairment can last from hours to days after use48 and potentially longer in heavy 
chronic users. Thus, the potential cognitive side effects of regular use of current Cannabis 
products are highly relevant to cancer patients, who may use Cannabis on a regular basis to treat 
their symptoms but who also want to maintain as much cognitive function as possible.  
2.1.5. Does CBD mitigate the harmful cognitive effects of THC? Clearly, the evidence 
suggests that acute Cannabis use is associated with at least modest cognitive impairment. 
However, almost all of this research was conducted with low potency cannabis provided by the 

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government and almost all of this research was focused on the effect of one particular 
cannabinoid, namely THC. The effects of other primary cannabinoids, such as CBD, are 
important to consider when interpreting the harmful effects of Cannabis use, especially given 
that Cannabis includes more than 80 additional phytocannabinoids57,58. Products commonly 
available in states like Colorado differ dramatically on the potency of these cannabinoids. As 
noted previously, studies suggest that THC is associated with memory and other cognitive 
impairment 48. Conversely, analyses suggest that CBD may attenuate the negative effects of THC 
on cognition and other measures59–68. Most of the work on CBD has involved the administration 
of THC and CBD in synthetic pill form. Much less is known about the combined effects of THC 
and CBD when using cannabis in the forms commonly available in dispensaries across the U.S. 
This is a high priority area of research in terms of understanding how to reduce the potentially 
harmful effects of cannabis use in cancer patients.  
2.1.6. Limitations of existing literature. Most of the Cannabis products that are sold in state 
regulated markets bear little resemblance to the products that are available for research from 
NIDA at the federal level in the U.S. For example, per Figure 169, the most recently available 
data in Colorado alone show that >600,000 edible units of Cannabis were sold across medical 
and recreational dispensaries each month of 2015, nearly a 50% increase from the monthly data 
reported for 2014, the first year of legal Cannabis sales in our state69. Data also suggest that 
medical Cannabis patients 
are more likely to use 
edible products than 
recreational users69. 
Importantly, using 
Cannabis in orally 
administered form 
represents a very different 
way to use cannabis, in 
part because in contrast to 
smoked forms of Cannabis 
which produce acute effects that begin to diminish rapidly after consumption (blood levels 
dramatically decrease within 15 minutes of smoking), orally administered Cannabis produces 
prolonged effects that last at least 4 hours post-consumption70,71. This in part explains their 
increased use in patients who seek sustained relief from symptoms. However, no data are 
available to understand the mechanisms or effects of orally administered Cannabis of various 
potencies and cannabinoid ratios. Thus, while the use of particular forms of Cannabis in cancer 
patients is supported by well-controlled clinical trials as reviewed above, very little is known 
about the efficacy, dose, routes of administration, or side effects of commonly available and 
increasingly used orally administered Cannabis products. In the case of cancer patients, our 
clinician co-investigators instruct their patients not to inhale Cannabis, but instead to use orally 
administered forms. More research is desperately needed given the increased availability of 
Cannabis across the nation and the lack of any research in the U.S. on the beneficial or harmful 
effects of orally administered Cannabis for cancer patients. 
 
Figure 1. State of Colorado Official Reporting on Edible Cannabis Sales 

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2.2 
RATIONALE  
2.2.1. Overview. We submitted a grant to NIH/NCI using an observational design that is well 
established by the CUChange Lab to do a fully powered trial with cancer patients. While the 
reviewers noted that “the proposed research will provide much needed scientific data to the 
public, physicians, patients, and to the larger research community on the varying effects of 
different forms of Cannabis on cancer treatment-related symptoms and patient quality of life” 
they were concerned that “while the group is experienced with the methodology proposed, the 
lung cancer population is a new endeavor. The team is bolstered by inclusion of coinvestigator 
effort with experience in this population, but there are no pilot data to indicate proof-of concept 
and feasibility of yielding a sufficient sample with reasonable compliance with procedures.” 
Thus, we seek to demonstrate proof-of-concept and feasibility. 
Our lab has been conducting neurobehavioral research on Cannabis39,72 as well as 
observational research on the relationship of Cannabis use to broader health behavior72–74 for 
many years. Recently, we have focused on the development of cutting edge observational 
designs to examine the effects of legal market cannabis in recreational and medical users. The 
goal of a fully powered version of this study would be to examine the effects of orally 
administered Cannabis on measures of symptom relief, quality of life, and cognitive function in 
the context of a human observational study of cancer patients. Our central hypothesis for a 
future, fully powered trial would be that the analgesic, anxiolytic, and somnolent effects of 
Cannabis will be strongly related to the potency ratio of the cannabinoids THC and CBD in 
the products participants select for use (i.e., products with a combination of THC and CBD 
as opposed to those with THC only will attenuate cognitive impairment, and also will be 
correlated positively with quality of life outcomes).” Thus, an observational study will provide 
concrete data to inform medical decision making and reduce the harm of Cannabis use in cancer 
patients. Note that in the current legal environment, and despite the fact that Cannabis use is 
legal in our state and nearly 30 other states, we are not permitted to handle Cannabis, have 
Cannabis in our research lab, nor provide Cannabis itself nor instructions for its use to research 
participants. Tightly controlled experimental laboratory studies (e.g., clinical trials with 
randomization) using products available in state-regulated markets are simply, at this point, not 
possible owing largely to federal law and the University requirements related to the Controlled 
Substances Act and Drug Free Schools and Communities Act. Because a traditional clinical trial 
design is not possible given the current federal status of Cannabis products, we would employ 
our established prospective observational design. Specifically, individuals who have already 
decided to try Cannabis for their cancer treatment-related symptoms will initiate use of an orally 
administered product they have selected. A research assistant will provide information on the 
range of edible Cannabis products and basic information about their various cannabinoid 
profiles, approximate prices, and nearby locations where participants may choose to purchase 
their product.   The participants will then purchase the product and decide how often and how 
much to use. This approach is consistent with federal law, supported by our preliminary and 
ongoing studies, and timely given that Cannabis is widely used by cancer patients in state 
legalized markets and yet almost no scientific data are available to aid cancer patients or their 
physicians in optimally prescribing medical Cannabis in this setting. An observational design 
that balances adequate internal validity with high external validity is critical for beginning to 
build the knowledge base about why so many cancer patients are turning to Cannabis. To that 

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end, we have developed and deployed innovative procedures that allow us to study legal market 
Cannabis in the compositions and forms that are widely available, while staying within the 
current regulatory framework and maintaining a high level of internal validity (see preliminary 
studies). Our purpose in future studies is to explore the pharmacological properties of THC, 
CBD, and their combination in orally administered cannabis with regard to differential impacts 
on symptom relief and cognition in order to understand and maximize any potential positive 
impact of Cannabis and minimize potential harm. Moving from our prior studies in recreational 
users to a cancer patient population has required an evolution in our research approaches, 
including addressing rapidity of accrual in a symptomatic population, together with capturing co-
medications, anti-cancer therapies and outcomes from these therapies as potential confounders of 
symptomatic and cognitive effects. Our studies will provide much needed scientific data to the 
public, physicians, patients, and to the larger research community on the varying effects of 
different forms of cannabis on cancer treatment-related symptoms and patient quality of life. Our 
proposed research is innovative and significant for the following reasons: 
2.2.2. Opportunity to examine orally administered Cannabis products in a state with 
legalized medical and recreational use. We capitalize on a novel opportunity to examine 
effects of orally administered Cannabis products currently legally available to, and used in 
growing amounts by, individuals with cancer. As reviewed, prior human clinical and laboratory 
work on the effects of Cannabis on pain and anxiety has focused on short acting nabiximols in 
studies outside the U.S or on U.S. government grown Cannabis of very low THC potency and 
with no CBD, which is smoked or vaporized. It is important to note that there is no federal 
source of orally administered Cannabis products for research, despite the fact that >600,000 
edible units are sold in Colorado alone every month. Given federal laws, the only way to conduct 
research on this widely consumed product is a naturalistic design, employing legal market orally 
administered products. Thus, although this study does NOT meet the definition of an 
interventional clinical trial per FDA guidelines, our observational design balances adequate 
internal validity with high external validity to result in a unique capacity to directly inform 
individual and policy decisions. This design is the only path forward in terms of understanding 
the effect of Cannabis in cancer patients because an actual clinical trial with edible Cannabis 
would never be allowed given the current legal environment at the federal level. 
2.2.3. Despite clinical data suggesting that certain forms of Cannabis are associated with 
reduced pain and other symptoms, there is a dearth of data on the mechanisms and effects 
of widely available forms of medical Cannabis with varying Cannabis potencies and 
cannabinoid ratios. Specific to pain, clinical data support nabiximols, which is a short acting 
Cannabis-based oral mucosal spray that combines THC and CBD, for pain relief. However, 
Cannabis users have a range of options that may vary in their benefits and harmful side effects, 
and importantly many cancer patients use Cannabis without obtaining a medical card nor 
receiving advice from a physician because Cannabis is easily purchased in recreational 
dispensaries. To our knowledge, there are no human studies in the literature that report the 
effects of legally available orally administered Cannabis in cancer patients, nor are there any 
reports in the literature of how various types of Cannabis may differentially impact pain, other 
symptom areas, and cognitive side effects in cancer patients. Using legal market orally 
administered Cannabis products  will provide new, externally valid, and more reliable 
assessments of the relationship of THC and CBD to both the potential beneficial and harmful 
effects of Cannabis. This research thus fills an important gap in the knowledge base on the 
effects of primary cannabinoids on symptom relief in cancer patients.  

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2.2.4. Addresses the need for timely empirical data on the harms and benefits of Cannabis 
use in cancer patients in order to impact public health. Given the extremely high rates of use 
of Cannabis in cancer patients, data on potential benefits and harms related to Cannabis use in 
this patient group are critical. An evidence-based message clearly describing the potentially 
beneficial effects on pain, anxiety, and sleep, as well as any harms related to cognitive effects of 
specific forms or compositions of Cannabis is needed, given the growing perception that 
Cannabis use is beneficial and is relatively safe. It is likely that not all Cannabis is equal in 
terms of harms or benefits. The proposed research will help begin to generate the evidence-base 
as to which forms, if any, produce the most direct effects on symptom domains as well as which 
forms produce the most harmful effects on cognition. Successful dissemination of this 
information to the public can directly inform patient decisions about whether to use Cannabis at 
all and which type to use.  
2.2.5. Preliminary studies relevant to this proposal.  
Prior experience and expertise of the team. The research team has taken a transdisciplinary 
approach to the study of the risks and benefits of Cannabis use across a number of populations. 
The PI (Bryan) and major Co-I (Bidwell) are co-directors of the CUChange Lab at the University 
of Colorado Boulder and have extensive experience in the integration of neurocognitive 
assessments into longitudinal behavioral research on substance use (e.g., R01 AA017390: PI 
Bryan; 2R01AA013844: PI Bryan; R01 DA025074: site PI Bidwell, Co-I Bryan; R01AA024632: 
Co-I’s Bidwell and Bryan; R01DA039707: Co-I’s Bidwell and Bryan). The PI also brings a 
wealth of statistical expertise. Co-I Camidge, who is a renowned clinical scientist and thoracic 
oncologist with medical expertise in the detection, treatment, and palliative care aspects of lung 
and other thoracic cancers, will serve as the medical director on the project. His medical 
oversight will be supported by Co-I Bowles, who has considerable expertise in the role of 
medical Cannabis in cancer patients. Drs. Camidge and Bowles are faculty at the University of 
Colorado Anschutz School of Medicine. Together, they authored a paper on the use of Cannabis 
in cancer care10..  
Previous and Current Cannabis Studies in the CUChange Lab. Our neurobehavioral research on 
Cannabis75,76 as well as observational research on the relationship of Cannabis use to broader 
health behavior is well documented12,72–74. One pilot study utilized a design similar to the one 
proposed in this application. In the pilot study, regular Cannabis users (n=22) were asked to 
switch strains for three days after a washout period. Participants used either a +THC/-CBD 
(~14% CBD, <1% CBD) or a +THC/+CBD (7% THC, 14% CBD) smoked strain that was 
acquired from a local dispensary. Both the researchers and participants were blind to condition, 
and the blind was maintained by the dispensary and one senior investigator. After the washout 
period of no Cannabis use, participants used the assigned Cannabis strain daily for three days, 
including a final use on the third day. Immediately after this final use, participants came to the 
lab, by taxi, for assessment of its effects on cognitive responses. Our data (Figure 2) suggest that 
CBD may mitigate the negative effects of THC on verbal recall12. 

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University of Colorado Thoracic Oncology Program. The program cares for close to 1000 
patients in total at the University of Colorado Hospital (UCH) and sees approximately 400 new 
thoracic oncology patients a year. In 2017, an informal survey in the clinic suggested 
approximately 40-50% of patients have tried medical Cannabis and 2 new medical Cannabis 
cards are being issued a month to this population. Although recall, nearly identical Cannabis 
products are available at recreational dispensaries to any adult 21 or over; thus, a medical card is 
not necessary. All aspects of clinical and translational 
research are well established in the program, with 
consistent rates of 30-40% of new patients engaged in 
classical interventional clinical trials. The main 
University of Colorado Hospital (UCH) is also associated 
with the largest VA in the Western region (set to move on 
site in 2018) and is part of a clinical network of hospitals 
across the Rockies front range run by UCHealth giving 
additional opportunities to explore to increase participant 
numbers as needed (see section 5.3.4). The study of 
Cannabis as an adjunct to palliative care approaches is 
thus critical and highly relevant to this patient group. 
 
 
2.3 
POTENTIAL RISKS AND BENEFITS  
 
2.3.1 KNOWN POTENTIAL RISKS  
 
• Human Subjects Involvement and Characteristics: Participants for the proposed research 
will be individuals who have been diagnosed with cancer of any solid tumor type and are 
interested in using Cannabis in the context of their cancer care. Participants’ medical 
charts will be reviewed by our study physician, with the documented consent of the 
patient participant, to ensure their safety to engage in study participation. To account for 
expected attrition (20-25% based on our similar Cannabis studies) 150 participants will 
be recruited in total, though we anticipate that only 30 of these will complete the study.  
• Sources of Materials: The source of the majority of research data will be the participants’ 
responses to questionnaires or questions on interviews. Other research data will involve 
cognitive tests. Finally, we will obtain information on health status and current 
medications from HIPAA compliant review of electronic medical records accessed by the 
study team and our oncology co-investigators. 
• Potential Risks: Potential risks are minimal. They include: a) Breach of confidentiality; 
b) Adverse effects of Cannabis such as intoxication, acute mood shifts, odd perceptual 
experiences, etc.; and c) The need for medical oversight in a cancer patient population. 
 
2.3.2 KNOWN POTENTIAL BENEFITS  
 

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The risks to participants are reasonable in relation to the anticipated benefits to participants and/or 
society, and in relation to the importance of the knowledge that may reasonably be expected to 
result, thereby falling in favor of performing the study: 
 
• To Participant: This study is expected to add to the knowledge base of 
information on the effects of different types of Cannabis and cannabinoids on 
cancer-related symptoms, quality of life, and cognition and are expected to inform 
patient choices and future harm reduction efforts. Given only a slight risk to 
participants and the greater possibility of long-term benefits to the scientific and 
public knowledge bases and providing highly externally valid data to inform harm 
reduction efforts, the risks/benefits ratio seems reasonable. The risks associated 
with participating have been minimized via procedures described above.  
• To Society: From a larger perspective, the findings of this investigation will 
increase the body of knowledge about the potential benefits and risks of orally 
administered legal market Cannabis use in cancer patients with any solid tumor 
type. Existing research on the connection between Cannabis and cancer related 
processes has used either animal models with extracted constituents of Cannabis 
(which is not how it is used by humans) or has focused on low potency forms 
and/or forms of Cannabis not typically used or available to U.S. residents, but are 
silent in several important ways. First, such studies are completely silent on the 
effects of orally administered Cannabis in forms widely available to cancer 
patients across the U.S. In addition, limited information is available on the impact 
of various potencies and the different components of the Cannabis used. We also 
have limited data on the impact of these legal market Cannabis products on 
cognitive functioning in cancer patients with any solid tumor type.  
• Justify the importance of the knowledge: Ultimately, the proposed study will add 
critical information to the knowledge base and provide an evidence-base that will 
inform personal decisions and reduce harm in patients who are considering using 
Cannabis in the context of their cancer treatment. In addition, these studies will 
allow for the development of public policy approaches to harm reduction, which 
is much needed in states that are legalizing Cannabis use for either medicinal or 
recreational purposes. 
 
3 
OBJECTIVES AND PURPOSE 
The goal of this study is to determine the feasibility of a human observational study of orally 
administered Cannabis use among cancer patients with any solid tumor type, towards developing 
feasibility/pilot data in support of an R01 grant application to the National Cancer Institute. The 
primary objective will be to demonstrate the number of contacts necessary to enroll 30 eligible 
patients and demonstrate reasonable compliance with study procedures (see section 10.5.4) 
within fifty-four months of active recruiting.  
 

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4 
STUDY DESIGN AND ENDPOINTS 
4.1 
DESCRIPTION OF THE STUDY DESIGN 
Tightly controlled experimental laboratory studies (e.g., clinical trials with randomization) 
using Cannabis products available in state-regulated markets are simply, at this point, not 
possible owing largely to federal law and the University requirements related to the Controlled 
Substances Act and Drug Free Schools and Communities Act. Because a traditional clinical trial 
design is not possible given the current federal status of Cannabis products, we will use a 
patient-oriented, prospective observational design. Specifically, individuals who have already 
decided to try Cannabis for their cancer treatment-related symptoms will initiate use of an orally 
administered product they have selected. A research assistant will provide information on the 
range of edible cannabis products and basic information about their various cannabinoid profiles, 
approximate prices, and nearby locations where participants may choose to purchase their 
product.   The participants will then purchase the product and decide how often and how much to 
use. This approach is consistent with federal law and supported by our preliminary and ongoing 
studies77 (1R01AT009541-01, 1R01DA044131-01, CDPHE2902, R01DA039707). Participants 
will take the product as they see fit, without any frequency or dosing instructions from study 
staff, for two weeks, at which time they will be scheduled for their Pre- and Post- Administration 
Assessment (Ta1-Tc1) so that we may examine the acute effects of the product. The final follow-
up will be one month later via an online survey sent directly to the participant via email. Details 
about the various study sessions are provided in Section 7.  
 
4.2 
STUDY ENDPOINTS 
 
4.2.1 PRIMARY ENDPOINT 
 
Our study endpoints are recruitment based. Please refer to the figure below.  
 
 
 
5 
STUDY ENROLLMENT AND WITHDRAWAL 
5.1 
PARTICIPANT INCLUSION CRITERIA 
In order to be eligible to participate in this study, an individual must meet all of the following 
criteria: 
Number of 
interested 
patients 
who 
contact the 
research 
team 
Number of 
eligible 
potential 
participants
Number of 
enrolled 
eligible 
participants
Number of 
timepoints 
completed 
by enrolled 
participants
Number of 
participants 
who 
complete 
the study

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1. Provision to sign and date the consent form. 
2. Stated willingness to comply with all study procedures and be available for the duration 
of the study. 
3. Be a female or male aged at least 21 years. 
4. Have a diagnosis of any solid tumor type who has or is undergoing either curative or 
palliative treatment. 
5. Have intent to use Cannabis to treat their symptoms. 
 
5.2 
PARTICIPANT EXCLUSION CRITERIA 
An individual who meets any of the following criteria will be excluded from participation in this 
study: 
1. Report of other non-prescription drug use, such as cocaine, heroin, methamphetamine in 
the past 60 days 
2. Actively seeking or in treatment for any substance use disorder 
3. Acute illness other than cancer that could affect cognition or compliance per the decision 
of the study M.D. 
4. Premenopausal females who are pregnant or trying to become pregnant. Participants who 
become pregnant while participating in the study will also no longer be eligible for 
participation. 
5. A Telephone Interview for Cognitive Status (TICS) score indicating moderate or severe 
cognitive impairment at screening 
 
5.3 
STRATEGIES FOR RECRUITMENT AND RETENTION 
5.3.1. Recruitment. With assistance from our Medical Director and co-investigator Dr. Camidge 
and co-investigator Dr. Bowles, we will advertise our study with flyers in local oncology clinics 
affiliated with the University of Colorado Health (UCHealth) system. Our partner oncologists 
will not actively recruit or consent study participants, but rather contribute by making patients 
aware of the opportunity to participate in this research. Flyers will also be posted in local 
oncology clinics not affiliated with UCHealth. Paid advertisements through Facebook and other 
social media sites that allow for targeting based on age, geographic location, and interests will be 
used. We will also utilize targeted mailings. A list of names and addresses of individuals who fit 
our age demographic and geographical area will be obtained from publicly available records 
purchased from a marketing firm (http://www.alescodata.com/reseller-programs.html). The 
recruitment flier will be mailed to each address on the list. In addition, print advertisements in 
local newspapers and magazines will be used. In terms of minority inclusion, the percentage of 
ethnic groups in the study will reflect the demography of the UCHealth Cancer clinics. 
Specifically, approximately 74% of participants will be non-Hispanic white, 12% will be 
Hispanic/Latino, 5% will be African American, and the remaining participants will be Asian, 
Native American/American Indian, or of mixed or other race. With respect to the recruitment of 
women, approximately 50% of cancer patients at UCHealth are female (51.4%). In terms of the 
inclusion of children, this is a study of the influence of Cannabis use on cancer care-related 
symptoms and cognitive function among cancer patients. Because the legal age for Cannabis use 
in Colorado is 21, we will not include any children in this project.  

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5.3.2. Participant Selection. A trained research assistant will screen prospective participants 
who call in for the study according to the inclusion/exclusion criteria. If any subject is 
questionable for inclusion, Dr. Bidwell (a licensed clinical psychologist) and Dr. Camidge (a 
licensed M.D.), will make the final determination of eligibility. Finally, all female potential study 
participants of child-bearing age will undergo a pregancy test to confirm eligibility. For the 
pregnancy screening, a trained research assistant will deliver a urine receptacle to the 
participant’s home. The participant will then use the restroom in their home and return the 
receptacle to the research assistant to complete the urine test in the mobile laboratory.We expect 
that the proposed studies will reflect the ethnic diversity of the cancer population at the Cancer 
Center at Anschutz School of Medicine, such that approximately 20-30% of the final sample will 
represent Latino and non-Caucasian individuals. 
5.3.3. Informed Consent. Potential participants who meet inclusion criteria will be scheduled 
for a remote baseline session. Participants will be emailed the eConsent in advance of this 
session. The eConsent may be viewed in its entirety and may be accessed at a later date if they 
want to think about participation. Each participant will go through the informed consent process 
with a trained research assistant over the phone or via Zoom, which will include reviewing all 
sections of the form, and answering any questions patients may have about study procedures or 
processes. Should participants choose to participate, they will verbally confirm that they agree to 
be in the study and will document informed consent electronically on the eConsent. Participants 
will be given the option of printing, downloading, or having the research team mail them a copy 
of the signed consent form for their own records. The REDCap e-consent framework will be 
used to document informed consent. The research assistant obtaining informed consent will 
electronically sign a separate instrument in REDCap associated with that participant’s record to 
document the informed consent process. 
5.3.4. Incentives and Retention. Our recruitment plan is to include patients with a diagnosis of 
any solid tumor type who has or is undergoing either curative or palliative treatment. However, 
because patients are not currently asked about their desire to use cannabis by their clinicians, and 
clinicians currently only know about patients’ cannabis use desires if they are asked to sign an 
authorization for medical use, we are not certain that our recruitment goals are obtainable. A 
second potential pitfall is that a cancer patient population is cognitively and medically 
vulnerable, so it is possible that our assessments may be too taxing in terms of length or duration 
for patients to comfortably complete. We have ordered and scheduled assessments in this 
feasibility study prioritizing measures that would be representative of primary outcomes in a 
fully powered study to be collected first should patients fatigue and wish to quit. If it becomes 
clear that the number or order of assessments is not feasible, we will assure that procedures are 
adjusted to minimize burden on our patient participants. Incentives are offered at three different 
time points in the study (see Table 7.1 for compensation rates at Baseline, Two-week Acute Use, 
and One-Month Online Follow-Up appointments).  
 
5.4 
PARTICIPANT WITHDRAWAL OR TERMINATION 
5.4.1 REASONS FOR WITHDRAWAL OR TERMINATION 
Participants are free to withdraw from participation in the study at any time upon request. An 
investigator may terminate participation in the study if any clinical adverse event (AE), laboratory 
abnormality, new pregnancy, or other medical condition or situation occurs such that continued 

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participation in the study would not be in the best interest of the participant. Though highly 
unlikely, other circumstances under which a participant would be withdrawn without her consent 
include: (1) obviously not following study instructions (note: we will carefully track the number 
of participants who do not or cannot follow instructions as this is critical for feasibility and the 
design of the fully powered trial) or (2) behaving in a way that is verbally or physically abusive 
towards research staff. Those who experience early withdrawal will receive prorated payment 
based on the number of sessions they completed. 
 
5.4.2 HANDLING OF PARTICIPANT WITHDRAWALS OR TERMINATION 
All procedures in this study are completely voluntary, and participants may withdraw their consent 
to participate at any point. Attempts will be made to understand why participants withdraw, as this 
is important for a feasibility trial, but even in that case giving investigators information concerning 
withdrawal is voluntary. Termination of participant by investigators, as described above, will also 
be tracked in case there are procedures that are not feasible for cancer patients to follow. Again, 
this is critical for a feasibility trial. Once participants withdraw or are terminated, there will be no 
attempt to follow up with or further engage with the participant. 
 
5.5 
PREMATURE TERMINATION OR SUSPENSION OF STUDY (STUDY 
STOPPING RULES) 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to the funding agency and 
regulatory authorities. If the study is prematurely terminated or suspended, the PI will promptly 
inform the IRB and will provide the reason(s) for the termination or suspension. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to participants. 
• Insufficient compliance to protocol requirements. 
• Data that are not sufficiently complete and/ or evaluable. 
• Determination of futility. 
 
6 
STUDY AGENT 
6.1 
STUDY AGENT(S) AND CONTROL DESCRIPTION 
 
6.1.1 ACQUISITION 
Study staff will not acquire orally administered Cannabis. The proposed work will utilize a 
design that is observational and does not involve assignment by the research team. More 
specifically, participants who are already planning to try Cannabis will choose their own product 
at baseline and purchase the product at a dispensary. Colorado law requires all edibles to be 

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tested by a state lab, which allows us to have a precise measure of potency after the participants 
purchase their products. Importantly, the researchers who conduct the assessments as well as all 
the senior investigators including the statistician (PI Bryan) will be blind to the participant’s 
product choice.   
 
6.1.2 FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
 
According to Colorado state law, we cannot relabel the packaging of any Cannabis product.  
 
6.1.3 DOSING AND ADMINISTRATION 
 
The patient will use their orally administered Cannabis ad libitum at home. This aspect of the 
design is again consistent with an observational design and differentiates it from a classical 
interventional clinical trial, which is critically important because it is the only path forward for 
research on orally administered, legal market Cannabis given current federal law. Study staff 
will not advise participants on or participate in dosing and administration practices.  
 
The disadvantage of our observational design is that we do not have direct control over the 
choice of product or the dosing and administration of the Cannabis product. To address this 
limitation, we will have participants take and send a picture of their purchased oral cannabis 
product to our lab via the REDCap system. Colorado requires all strains to be tested by a state 
licensed lab, and the dispensary that we work with performs cannabinoid and terpene potency 
testing on each batch produced and sets aside a specific lot of strains corresponding to the ratios 
utilized in this project (a CBD-dominant strain, a THC-dominant strain, and a THC+CBD 
strain). Thus, having a picture of the participant’s purchased product will allow us to verify the 
strain and thus, the ratio of cannabinoids contained in the product for a measure of potency to 
operationalize our user groups.  
 
 
6.1.4 ROUTE OF ADMINISTRATION 
Oral administration ad libitum 
 
6.1.5 STARTING DOSE AND DOSE ESCALATION SCHEDULE 
Starting dose and escalation ad libitum 
 
 
6.1.6 DURATION OF THERAPY 
Two weeks use ad libitum 
 
7 
STUDY PROCEDURES AND SCHEDULE 
7.1 
STUDY PROCEDURES/EVALUATIONS 

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The complete schedule of measures taken at each assessment are outlined in Table 7.1.  
 
Table 7.1: Schedule of Locations and Assessments 
Timepoint 
Measures 
 
Location 
Compensation 
Baseline (T00) 
Pain interference, pain intensity, anxiety symptoms, 
state and trait anxiety, sleep, quality of life, objective 
cognition, subjective cognition, demographics, 
alcohol and substance use history, cancer 
staging/treatment regimen (EMR) 
 
At home 
(online) 
$60, 1.5 hours 
Two weeks ad 
libitum use 
 
At home 
 
Pre-acute 
Cannabis use 
(Ta1) 
Pain interference, pain intensity, anxiety symptoms, 
state and trait anxiety, sleep, quality of life, objective 
cognition, subjective cognition, alcohol and substance 
use history(timeline follow-back). 
 
At home 
(online) 
 
1 hour post-
acute Cannabis 
use (Tb1) 
Pain intensity, state anxiety, objective cognition 
At home 
(online) 
 
2 hour post-
acute Cannabis 
use (Tc1) 
Pain intensity, state anxiety, objective cognition 
At home 
(online) 
$100, 2.5 
hours 
One month 
follow-up 
(M1) 
Pain interference, pain intensity, anxiety symptoms, 
state and trait anxiety, sleep, quality of life, subjective 
cognition, other substance use, Disease 
status/treatment regimen (EMR) 
 
At home 
(online) 
$10, 20 
minutes 
NOTES: EMR=electronic medical record, total compensation possible for 4 hours, 20 minutes of assessment=$170 
 
 
 
 
 
 
 
7.2 
LABORATORY PROCEDURES/EVALUATIONS 
The complete list of measures and procedures is detailed in Table 7.2 below. 
 
Table 7.2: Study Measures 
Domain 
Measure 
Pain interference 
REDCap: Promis Pain Interference CAT 
Pain intensity 
REDCap: Pain Intensity 
Anxiety symptoms 
Beck Anxiety Inventory (BAI) 

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State and trait anxiety 
State-Trait Anxiety Inventory (STAI) 
Sleep 
Pittsburgh Sleep Quality Index (PSQI) 
Quality of life 
Functional Assessment of Cancer Therapy - General (FACT-G) 
Objective cognition 
Telephone Interview for Cognitive Status (TICS) 
Neurocognitive battery targeting executive function* 
Subjective cognition 
Functional Assessment of Cancer Therapy – Cognitive Function 
(FACT-Cog) 
Substance Use History 
Marijuana Consumption Questionnaire (MCQ) 
Alcohol Use Disorder Identification Test (AUDIT) 
Timeline Follow-Back (TLFB) 
 
 
*Tests for which deficits have been observed previously among cancer patients 78–80 and include measures that are recommended 
by the International Cancer and Cognition Task Force 
 
 
7.2.1 CLINICAL LABORATORY EVALUATIONS (RESEARCH 
PROCEDURES) 
 
 Pregnancy screening. A urine pregnancy screening test will be administered to all female 
potential study participants of child-bearing age after informed consent has been obtained at the 
Baseline visit to verify eligibility for the study. For the pregnancy screening, a trained research 
assistant will deliver a urine receptacle to the participant’s home. The participant will then use 
the restroom in their home and return the receptacle to the research assistant to complete the 
urine test in the mobile laboratory. 
 
 
7.2.2 OTHER ASSAYS OR PROCEDURES (RESEARCH) 
 
Pain Intensity and Pain interference. We employ two self-report measures of pain intensity 
and interference. Pain Intensity consists of one item asking about the participant’s level of pain 
in the past seven days. Participants are asked to rate their pain on a scale from 0 (no pain) to 10 
(worst imaginable pain). The Promis Pain Interference CAT asks participants about how their 
experience of pain interfered with or affected their enjoyment of various daily activities in the 
past seven days. The scale is computer-adapted and has a minimum of four questions and a 
maximum of 12 questions.  
Anxiety and Mood Disturbance. The primary measure of lasting effects of Cannabis anxiety, 
the Beck Anxiety Inventory (BAI)82 consists of 21 items, each describing a symptom of anxiety. 
Secondary assessments of anxiety and mood disturbance include the Positive and Negative 
Affect Schedule (PANAS), a brief, reliable and valid measure of positive and negative affect83 
and the Beck Depression Inventory-II (BDI-II) consisting of 21 scaled statements designed to 
assess symptoms of depression84. As its name suggests, the State-Trait Anxiety Inventory 
(STAI)85 assesses both trait and state anxiety.  
Sleep. Perceived sleep quality will be assessed by the commonly-used and well-validated 
Pittsburgh Sleep Quality Index86. 
Quality of Life. A commonly-used quality of life measure specific to cancer patients will be 
used to assess perceived quality of life: the Functional Assessment of Cancer Therapy - General 

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(FACT-G)87 assesses aspects of quality of life specific to cancer patients, including physical 
(e.g., nausea, lack of energy), social, emotional, and cognitive well-being88.  
Objective and Subjective Cognitive Functioning. The Telephone Interview for Cognitive 
Status (TICS) will be used at screening to assess for moderate to severe cognitive impairment 
that would preclude enrollment as a study participant. The TICS is a widely used and validated 
measure of cognitive impairment that is highly correlated to the Mini Mental State Exam 
(MMSE) 89. To assess objective cognitive functioning, we will conduct a neurocognitive battery 
on all participants that targets executive function. We will conduct this battery using Tatool, an 
open-source software developed to run psychological experimental studies90. This battery 
includes tests for which deficits have been observed among cancer patients78–80 and include 
measures that are recommended by the International Cancer and Cognition Task Force91. The 
battery covers the domains found to be sensitive to the effects of Cannabis 55. Specifically, the 
cognitive battery will include the Stroop Task92 to assess inhibition and the Shape/Color Shifting 
Task93 to assess shifting. We will assess subjective cognitive functioning with the Functional 
Assessment of Cancer Therapy – Cognitive Function (FACT-Cog), a reliable and valid 
assessment of perceived cognitive functioning specifically designed for cancer patients94. 
Health/Disease Status and Treatment Regimen. With the assistance of our oncology 
collaborators and OCRS staff, and with explicit informed consent from our patient participants, 
we will access Electronic Medical Records (EMRs) via the Health Data Compass95 coinciding 
with the Baseline encounter and the One Month Follow-up. We will obtain data regarding cancer 
staging, tumor characteristics, treatment regimen (observation versus chemotherapy, targeted 
therapy, immunotherapy, combination of therapies, or other), current medications and doses 
(including treatment-supporting medications only), and any co-existing conditions.  
Substance Use History.  The Marijuana Consumption Questionnaire (MCQ)96 is used to collect 
information on the frequency and quantity of cannabis use, age of first use, peer use, perceived 
risk from Cannabis, and perceived availability of Cannabis. The Alcohol Use Disorder 
Identification Test (AUDIT)97 will be used to examine the extent of alcohol use and problems 
related to alcohol use. A Timeline Follow-Back (TLFB) will be used to assess daily substance 
use for the 30 days prior to the baseline session and for the 14 days prior to the 2-week pre-acute 
use session98. The TLFB is a calendar assisted structured interview that provides a study 
participant with temporal cues to increase the accuracy of recall. This instrument has 
demonstrated test-retest reliability and validity99 
Demographics. Personal information including gender, age, detailed race/ethnicity, and SES 
will be collected by self-report in addition to extraction from the EMR obtained via Health Data 
Compass.  
Pregnancy Screening. A urine pregnancy screening test will be administered to all female 
potential study participants of child-bearing age after informed consent has been obtained at the 
Baseline visit to verify eligibility for the study. For the pregnancy screening, a trained research 
assistant will deliver a urine receptacle to the participant’s home. The participant will then use 
the restroom in their home and return the receptacle to the research assistant to complete the 
urine test in the mobile laboratory. 
 
 
 

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7.3 
STUDY SCHEDULE 
 
7.3.1 SCREENING 
 
A trained research assistant will screen prospective participants who call in for the study 
according to the inclusion/exclusion criteria. Research assistants will also provide an explanation 
of the study timeline and schedule of assessments, and compensation during this call, and answer 
any questions that participants may have about participation. If any subject is questionable for 
inclusion, Dr. Bidwell (a licensed clinical psychologist) and Dr. Camidge (a licensed M.D.), will 
make the final determination of eligibility. If a patient is deemed eligible for participation and 
wishes to proceed, an appointment will be made for a Baseline remote session. All female 
potential study participants of child-bearing age will then be asked to participate in pregancy 
testing to verify eligibility. A trained research assistant will deliver a urine receptacle to the 
participant’s home. The participant will then use the restroom in their home and return the 
receptacle to the research assistant to complete the urine test in the mobile laboratory. 
 
 
7.3.2 ENROLLMENT/BASELINE 
 
Potential participants who meet inclusion criteria will be scheduled for a baseline session. A 
trained research assistant will meet remotely with the participant via phone or Zoom. Each 
participant will go through the informed consent process. Once consented, participants will 
complete current and historical health and substance use assessments and cognitive testing (see 
Table 7.1). Participants will complete assessments via emailed, individually tailored links hosted 
by and integrated into the study’s REDCap databases (https://redcap.ucdenver.edu/). Participants 
will then receive a consultation from research staff on the range of edible Cannabis products and 
basic information about their various cannabinoid profiles, approximate prices, and nearby 
locations where participants may choose to purchase their product. Again, research staff will not 
advise study participants to purchase any specific product. Participants will be compensated with 
a $60 grocery store gift card for their time and effort at the end of the visit, which will be mailed 
to their home. 
 
7.3.3 FOLLOW-UP  
 

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Ad Libitum Cannabis Administration at 
Home. The participant will use their orally 
administered Cannabis ad libitum at home. This 
aspect of the design differentiates the proposed 
research from a classical interventional clinical 
trial, which is critically important because it is 
the only path forward for research on orally 
administered, legal market Cannabis given 
current federal law. It is well known in the pain 
and broader medication literatures that 
expectancies regarding the effects of a 
medication have profound influences on the 
patient experience of symptom reduction 100,101. 
Colorado requires all orally administered Cannabis products to be tested by a state lab, which 
allows us to have a precise measure of potency despite the inability to assign products to users. 
While participants are not blind to the type of product they are ingesting, it is important to note 
that the subjective effects of THC and CBD are quite different59–62,64–68,102, and thus participants 
who are not naïve to Cannabis use would likely not be blind even if assigned to a product. 
Importantly, the researchers who conduct the assessments as well as most of the senior 
investigators will be blind to condition. The observational aspect of the design involves the 
instruction to use their selected product at home consistent with the packaging directions and/or 
as they see fit. Consistent with federal law, study staff will not provide any directions regarding 
dosing and administration. For verification purposes, participants will take and send a picture of 
their purchased product to the CUChange Lab via the REDCap system as mentioned in section 
6.1.3. 
 
Pre- and Post- Administration Assessment (Ta1-Tc1). The Pre- and Post- Administration 
Assessment will take place two weeks (+/- 4 days) following the baseline session. A trained 
research assistant will meet remotely with the participant via phone or Zoom. Links to 
assessments will be emailed to the participannt at the start of the session. Prior to taking their 
Cannabis, participants will complete self-report assessments, including those assessing 
quantity/frequency of Cannabis use and symptom severity over the prior two weeks (Ta1). They 
will then consume their orally administered Cannabis. Because 60 minutes is the average time 
that CBD and THC levels begin to peak in the blood after oral administration of Cannabis 
extract70,71, assessments of the acute effects of Cannabis (see Table 7.2) will begin one hour (+/- 
5 minutes) post-edible consumption (Tb1). After peak, levels steadily decrease over the next 2-3 
hours and by 4 hours post-ingestion begin to rapidly drop off in blood70,71. To account for 
individual differences in metabolism and sensitivity, participants will be assessed again at 2 
hours (+/- 5 minutes) post-consumption (Tc1). After completing the 1- and 2- hour post-
consumption assessments,, participants will receive a $100 grocery store gift card as 
compensation for their time and effort, which will be mailed to their home. 
 
7.3.4 FINAL STUDY VISIT 
 
Figure 3. Example of an edible Cannabis product 

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At the end of the Pre- and Post- Administration Assessment, participants may elect to 
continue use of the same product, switch to another product, or discontinue their Cannabis use. 
While the main observational portion of the study will be complete at that point, we will follow-
up with participants in regard to their symptoms levels, Cannabis use, and cognition, using an 
online survey one month (+/- 7 days) later (M1), in keeping with the observational nature of the 
design. This aspect will provide important data on feasibility of longer-term follow-up with this 
population, and further valuable data in regard to patient choice, patient behavior, patterns of use 
of Cannabis products, and associated experience of symptoms related to cancer treatment in a 
fully-powered iteration of the study. The survey will assess their Cannabis use, other substance 
use, symptom levels (pain, anxiety, and sleep), quality of life, and subjective and objective 
cognitive functioning over the past month. We also will conduct the final health status and 
treatment regimen review of the participant’s EMR separately at this time point via Health Data 
Compass. Participants will receive a $10 grocery store card as compensation for their time and 
effort, which will be mailed to their home. 
 
 
 
7.3.5 Schedule of Events Table 

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Table 7.3 Schedule of Events 
 
Demographics 
AEs 
 
MCQ 
AUDIT 
TLFB 
EMR Review 
Obj. Cognition 
Sub. Cognition 
FACT-G 
PSQI 
Anx-Mood (State) 
Anx-Mood (Trait) 
Pain (7 days) 
Pain (Right now) 
T00:  
Baseline 
X 
X* 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Ta1:  2-
Week 
Pre-Acute 
Use 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Tb1:  2-
Week 1-
Hour  
Post-
Acute Use 
 
X 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
Tc1:  2-
Week 2-
Hour  
Post-
Acute Use 
 
X 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
M1:  1-
Month 
Follow-
Up 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
MCQ = Marijuana Craving Questionnaire 
AUDIT = Alcohol Use Disorder Identification Test 
TLFB = Timeline Followback Substance Use Assessment 
Objective Cognition = Stroop task, Shape/Color Shifting Task. 
Subjective Cognition = Functional Assessment of Cancer Therapy – Cognitive Function (FACT-Cog) 
FACT-G = Functional Assessment of Cancer Therapy - General 
PSQI = Pittsburgh Sleep Quality Index 
Anx-Mood (Trait)= Beck Anxiety Inventory (BAI),  Beck Depression Inventory-II (BDI-II),  
Anx-Mood (State) = Positive and Negative Affect Schedule (PANAS), State-Trait Anxiety Inventory (STAI) 
Pain (7 days) = Pain Intensity (7 days), the Promis Pain Interference CAT 
Pain (Right now) = Pain Intensity (Right now) 
 
* The PI will record all reportable events with start dates occurring any time after informed consent is obtained until 7 (for non-serious AEs) or 30 days 
(for SAEs) after Tc1. 
 
 
8 
ASSESSMENT OF SAFETY 
8.1 
SPECIFICATION OF SAFETY PARAMETERS 
 

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8.1.1 DEFINITION OF ADVERSE EVENTS (AE) 
 
We define adverse event as “Any untoward or unfavorable medical occurrence in a participant, 
including any abnormal sign (e.g. abnormal physical exam or laboratory finding), symptom, or 
disease, temporally associated with the participants’ involvement in the research, whether or not 
considered related to participation in the research” 
(http://www.colorado.edu/vcr/sites/default/files/IRB%20Policy%20Procedures-%20Final%2010-
01-11_website.pdf).  
 
8.1.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE) 
 
We define serious adverse event as an event that “Results in death, is life threatening, or places 
the participant at immediate risk of death from the event as it occurred, requires hospitalization, 
causes persistent or significant disability or incapacity, or is another condition which investigators 
judge to represent significant hazards.”  
(http://www.colorado.edu/vcr/sites/default/files/IRB%20Policy%20Procedures-%20Final%2010-
01-11_website.pdf).  
 
8.1.3 DEFINITION OF UNANTICIPATED PROBLEMS (UAP) 
 
This study will use the Office of Human Research Protection (OHRP) definition of an 
unanticipated problem: “involving risks to participants or others to include, in general, any 
incident, experience, or outcome that meets all of the following criteria: 
• Unexpected in terms of nature, severity, or frequency given (a) the research procedures 
that are described in the protocol-related documents, such as the IRB-approved research 
protocol and informed consent document; and (b) the characteristics of the participant 
population being studied; 
• Related or possibly related to participation in the research (“possibly related” means there 
is a reasonable possibility that the incident, experience, or outcome may have been 
caused by the procedures involved in the research); and 
• Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized.” 
 
 
 
 
8.2 
CLASSIFICATION OF AN ADVERSE EVENT 
 
8.2.1 SEVERITY OF EVENT 
For AEs not included in the protocol-defined grading system, the following guidelines will be used 
to describe severity. 

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• Mild – Events require minimal or no treatment and do not interfere with the 
participant’s daily activities. 
• Moderate – Events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference with 
functioning. 
• Severe – Events interrupt a participant’s usual daily activity and may require 
systemic drug therapy or other treatment. Severe events are usually potentially life-
threatening or incapacitating. 
  
8.2.2 EXPECTED ADVERSE EVENTS  
 
Any medical condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE. Given the observational nature of our study 
and the disease state of our target participants, common events in our study population such as 
feeling intoxicated from marijuana, mild or consistent with baseline levels of pain, anxiety, 
drowsiness, or nausea are to be expected and will be documented on case report forms but not be 
reported as adverse events. 
 
8.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND 
FOLLOW-UP 
The occurrence of an AE or SAE may come to the attention of study personnel during study 
sessions. All AEs including local and systemic reactions 1) not meeting the criteria for SAEs, 2) 
not included in the list of expected events in Section 8.2.3, or 3) beyond a threshold for an expected 
event listed in Section 8.2.3 (such as greater than mild symptoms or significant change from 
baseline in pain, anxiety, drowsiness, or nausea) will be captured on the appropriate case report 
form by a CUChange Lab professional research assistant. Information to be collected includes 
event description, time of onset, assessment of severity, and time of resolution/ stabilization of the 
event.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the 
event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
 
At each study visit, the professional research assistant will inquire about the occurrence of AE/ 
SAEs since the last visit.  
 
8.4 
REPORTING PROCEDURES 
8.4.1 ADVERSE EVENT REPORTING  
The study team will adhere to the protocol detailed in the figure below for reporting adverse 
events. 

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The study team will record all reportable events with start dates occurring any time after 
informed consent is obtained until seven days after the last day of study participation. All AEs 
will otherwise be followed to adequate resolution or stabilization. 
 
8.4.2 SERIOUS ADVERSE EVENT REPORTING  
 
Since the study procedures are not greater than minimal risk, SAEs are not expected. Should an 
SAE occur, the study team will adhere to the protocol detailed in the figure below for reporting 
serious adverse events. 
 
The study team will record all reportable events with start dates occurring any time after 
informed consent is obtained until 30 days after the last day of study participation. All SAEs will 
otherwise be followed to adequate resolution or stabilization. 
 
8.4.3 UNANTICIPATED PROBLEM REPORTING  
 
Since the study procedures are not greater than minimal risk, UAPs are not anticipated. Incidents 
or events that meet the OHRP criteria for UAPs require the creation and completion of a UAP 
report form and including the following information: 
• Protocol-identifying information: protocol title and number, PI’s name, and the IRB 
project number; 
• A detailed description of the event, incident, experience, or outcome; 
• An explanation of the basis for determining that the event, incident, experience, or 
outcome represents a UAP; 
Research 
Assistant 
becomes aware 
of AE
PI Bryan and Co-
I Camidge 
receive notice of 
AE within same 
business day
Research 
Assistant 
submits formal 
AE 
documentation 
to Bryan and 
Camidge within 
24 hours of 
event
Submission of 
AE 
documentation 
will be made to 
IRB within 72 
hours of events
Research 
Assistant 
becomes aware 
of SAE
PI Bryan and Co-
I Camidge 
receive notice of 
SAE immediately
Research 
Assistant 
submits formal 
SAE 
documentation 
to Bryan and 
Camidge within 
8 hours
Submission of 
SAE 
documentation 
will be made to 
IRB within 24 
hours of events

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• A description of any changes to the protocol or other corrective actions that have been 
taken or are proposed in response to the UAP. 
 
To satisfy the requirement for prompt reporting, UAPs will be reported using the following 
timeline: 
• UAPs that are SAEs will be reported to the IRB within 24 hours of the investigator 
becoming aware of the event. 
• Any other UAP will be reported to the IRB within 72 hours of the investigator 
becoming aware of the problem. 
 
8.4.4 REPORTING OF PREGNANCY 
 
Patients who are pregnant or trying to become pregnant are ineligible for participation. If a 
participant becomes pregnant after enrolling in the study, the participant will be withdrawn. 
 
9 
CLINICAL MONITORING 
Clinical site monitoring will be conducted to ensure that the rights and well-being of human 
participants are protected, that the reported trial data are accurate, complete, and verifiable, and 
that the conduct of the trial is in compliance with the currently approved protocol/ amendment(s), 
with GCP, and with applicable regulatory requirement(s).  
 
Monitoring for this study will be performed by CU Cancer Center Clinical Monitor in accordance 
with the clinical monitoring plan (CMP), incorporated herein by reference. The CMP describes in 
detail who will conduct the monitoring, at what frequency monitoring will be done, at what level 
of detail monitoring will be performed, and the distribution of the monitoring reports. 
 
The principal investigator will be responsible for the conduct of this study, overseeing participant 
safety, executing the data and safety monitoring (DSM) plan, and complying with all reporting 
requirements to local and federal authorities. This oversight will be accomplished through 
additional oversight from the Data and Safety Monitoring Committee (DSMC) at the University 
of Colorado Cancer Center (CU Cancer Center).  The DSMC is responsible for ensuring data 
quality and study participant safety for all trials at the CU Cancer Center.   A summary of the 
DSMC’s relevant activities is as follows: 
• Conduct of internal audits 
• May submit recommendations for corrective actions to the CU Cancer Center’s 
Executive Committee 
 
Study audits conducted by the DSMC will consist of a review of the regulatory documents, 
consent forms, and source data verification.  Documentation of the audit conducted by the 
DSMC will then need to be submitted to the IRB of record at the time of the IRB’s continuing 
review of this trial (if applicable). 

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10 
STATISTICAL CONSIDERATIONS  
10.1 STATISTICAL AND ANALYTICAL PLANS 
This is a feasibility study and thus underpowered for meaningful analysis; the endpoints are 
strictly recruitment based. We will however examine the data for completeness (i.e., were any 
measures or items consistently left blank). In addition, we will examine the summary statistics 
including mean and standard deviation for continuous items as well as skew and kurtosis to 
evaluate whether the measures approximate a normal distribution. For categorical outcomes, we 
will examine proportions in each category to get some idea of variability on the measure. 
 
 
10.2 STATISTICAL HYPOTHESES 
• Primary Efficacy Endpoint(s): 
This section is not applicable. 
 
• Secondary Efficacy Endpoint(s): 
This section is not applicable. 
 
10.3 DESCRIPTION OF STATISTICAL METHODS 
10.3.1  
ADHERENCE AND RETENTION ANALYSES 
This feasibility study has an 80% retention goal for reasonable compliance with study procedures 
by enrolled study participants. Reasonable compliance is defined as 75% completion of study 
assessments. Adherence is not applicable to this observational study design. 
 
10.3.2  
BASELINE DESCRIPTIVE STATISTICS 
We will characterize the cohort based on demographics, disease stage, and other relevant 
descriptives. 
 
10.4 SAMPLE SIZE 
We plan to recruit 30 participants into this feasibility study, as we believe this will be adequate to 
determine whether the larger trial is possible and whether there are changes in study procedures 
that would be required before initiating a fully powered study. 
 

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10.5 MEASURES TO MINIMIZE BIAS 
The investigators and research assistants will be blind to Cannabis edible product condition. A 
member of the study team not responsible for data collection will maintain the experimenter 
blind. 
 
10.5.1 ENROLLMENT/ RANDOMIZATION/ MASKING PROCEDURES 
Participants will be free to select the edible Cannabis product of their choice and use their 
product ad libitum. They will report on their selection via an individualized, emailed REDCap 
survey blinded to the study team with the exception of a member of the study team not 
responsible for data collection. 
 
10.5.2 EVALUATION OF SUCCESS OF BLINDING  
Because we do not anticipate the blinding to be maintained by participants, we will not assess the 
success of the blind. 
 
10.5.3 BREAKING THE STUDY BLIND/PARTICIPANT CODE 
Since participants are aware of which product they are taking, there are no conditions under 
which the blind needs to be broken. 
 
11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS 
We have taken a number of measures to ensure the confidentiality of the data and the safety of 
the participants. All data from the proposed study will be identified by a numerical ID code only. 
The information linking the numerical ID code to identifying information will be maintained 
separate and secure from the data themselves. At the conclusion of the final data collection 
session, the list linking the ID code to identifying information will be destroyed.  
 
12 
QUALITY ASSURANCE AND QUALITY CONTROL 
The CUChange Lab has established standard operating procedures (SOPs) to ensure quality 
assurance (QA) in the design of databases for observational studies such as the proposed 
project. The data entry system has been well established with previous studies and relies on a 
strategy of centralized data capture through REDCap. Raw data is uploaded daily to REDCap 
either manually or through automated application programming interface (API) call. Professional 
research assistants review all case report forms and raw data at the conclusion of every study 
session or upon receipt of data from collaborators (such as cannabinoid lab results) as applicable. 
 
Quality control (QC) SOPs at the CUChange Lab include quarterly data review of 10 randomly 
selected participant records. This will be logged (who checked the data, what parts of the data 
were checked if not all assessments, when the data was checked, and if there are any outlying 

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issues or discrepancies to follow-up on, and who will follow-up with any discrepancies and 
when).  
 
The investigational team will provide direct access to all study-related sites, source data/ 
documents, and reports for the purpose of monitoring and auditing by the DSMC audit team, and 
inspection by local and regulatory authorities. 
 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS  
13.1 ETHICAL STANDARD  
The PI will ensure that this study is conducted in full conformity with regulations for the Protection 
of Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56.  
 
13.2 INSTITUTIONAL REVIEW BOARD  
The protocol, informed consent form(s), recruitment materials, and all subject materials will be 
submitted to the Colorado Multiple Institutional Review Board (COMIRB) for review and 
approval. Approval of both the protocol and the consent form must be obtained before any subject 
is enrolled. Any amendment to the protocol will require review and approval by COMIRB before 
the changes are implemented to the study. All changes to the consent form will COMIRB 
approved; a determination will be made regarding whether previously consented participants need 
to be re-consented. 
 
13.3 INFORMED CONSENT PROCESS  
Participants are informed of all procedures beforehand, and they must read and sign the eConsent 
stating that they understand and agree to the procedures before beginning the study. As part of 
this process, they are informed that they may withdraw from the study at any time. Acceptance 
into the study will be contingent on a review of current health status and health history by our 
study physicians (Co-Is Dr. Camidge and Dr. Bowles) to ensure that illness is not present at a 
level severe enough as to impede informed consent and/or participation in a research study. In 
addition, Dr. Bidwell (Co-I) will review the patient’s screening assessment of cognitive and 
psychological functioning, including the TICS score to ensure that there are no psychological 
comorbidities or cognitive deficits that impede decisional capacity, informed consent, and/or 
study participation.  
 
13.3.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS 
PROVIDED TO PARTICIPANTS 
eConsent forms describing in detail the study procedures, timeline, and risks are given to the 
participant and written online documentation of informed consent is required prior to starting 
participation in this observational study.  
 

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13.3.2 CONSENT PROCEDURES AND DOCUMENTATION 
 
The informed consent process will be initiated prior to the individual’s agreeing to participate in 
the study and continues throughout the individual’s study participation. Extensive discussion of 
risks and possible benefits of participation will be provided to the participants and their families.  
 
The eConsent will be IRB-approved and the participant will be asked to read and review the 
document. The professional research assistant will explain the research study to the participant and 
answer any questions that may arise. All participants will receive a verbal explanation in terms 
suited to their comprehension of the purposes, procedures, and potential risks of the study and of 
their rights as research participants. Participants will have the opportunity to carefully review the 
eConsent and ask questions prior to signing. The participants will have the opportunity to think 
about the study prior to agreeing to participate. The participant will sign the eConsent document 
prior to any procedures being done specifically for the study.  
 
The participants may withdraw consent at any time throughout the course of the trial. A copy of 
the eConsent document will be given to the participants for their records. The rights and welfare 
of the participants will be protected by emphasizing to them that the quality of their medical care 
will not be adversely affected if they decline to participate in this study. 
 
The study excludes non-English speakers.  
 
13.4 PARTICIPANT AND DATA CONFIDENTIALITY  
Participant confidentiality is strictly held in trust by the participating PIs, their staff, and the 
sponsor(s) and their agents. This confidentiality is extended to cover testing of biological 
samples and genetic tests in addition to the clinical information relating to participants. 
Therefore, the study protocol, documentation, data, and all other information generated will be 
held in strict confidence. No information concerning the study or the data will be released to any 
unauthorized third party without prior written approval of the sponsor-investigator. 
 
Authorized representatives of the sponsor-investigator and representatives of the IRB may 
inspect all documents and records required to be maintained by the investigator, including but 
not limited to medical records (office, clinic, or hospital) and case report forms for the 
participants in this study. The CUChange Lab will permit access to such records. 
 
The study participant’s contact information will be securely stored at the CUChange Lab for 
internal use during the study. At the end of the study, all records will continue to be kept in a 
secure location for as long a period as dictated by local IRB and Institutional regulations. 
 
Study participant research data, which is for purposes of statistical analysis and scientific 
reporting, will be transmitted to and stored at the University of Colorado Cancer Center. This 
will not include the participant’s contact or identifying information. Rather, individual 
participants and their research data will be identified by a unique study identification number. 
The study data entry and study management systems used by the CUChange Lab and by the 

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University of Colorado Cancer Center research staff will be secured and password protected. At 
the end of the study, all study databases will be de-identified and archived at the University of 
Colorado Cancer Center. 
 
 
13.4.1 RESEARCH USE OF STORED HUMAN SAMPLES, SPECIMENS OR 
DATA 
 
Intended Use: Samples and data collected under this protocol may be used to study the effect of 
Cannabis use among cancer patients. No genetic testing will be performed. Storage: Data will 
be stored using codes assigned by the investigators. Data will be kept in password-protected 
computers. Only investigators will have access to the samples and data. 
Tracking: Data will be tracked using REDCap. 
Disposition at completion of the study: Not applicable—no stored samples will be collected.  
 
 
14 
DATA HANDLING AND RECORD KEEPING  
14.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
Assessment data collection is the responsibility of the CUChange Lab study personnel under the 
supervision of the site PI. Data collected by EMR review will be the responsibility of the study 
team with the help of Drs. Camidge and Bowles and collaboration from the PI. The PI is 
responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data reported.  
 
All source, paper documents will be completed in a neat, legible manner to ensure accurate 
interpretation of data. When making changes or corrections, study personnel will cross out the 
original entry with a single line, and initial and date the change. Study personnel will NOT ERASE, 
OVERWRITE, OR USE CORRECTION FLUID OR TAPE ON THE ORIGINAL. 
 
Data reported in the REDCap electronic case report forms (eCRFs) derived from source documents 
should be consistent with the source documents/raw data, otherwise the discrepancies will be 
explained and captured in a progress note and maintained in the participant’s official electronic 
study record. Copies of the blank eCRF forms will be maintained for documentation purposes. 
 
Clinical data (including AEs and expected adverse reactions data) and clinical laboratory data will 
be entered into REDCap, a 21 CFR Part 11-compliant data capture system provided by the 
University of Colorado Denver. The data system includes password protection and internal quality 
checks, such as automatic range checks, to identify data that appear inconsistent, incomplete, or 
inaccurate. Clinical data will be entered manually directly from the source documents or through 
automated API call. 
  

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14.2 STUDY RECORDS RETENTION  
Study documents should be retained for a minimum of two years after the final participant has 
completed the study. These documents should be retained for a longer period, however, if required 
by local regulations, or institution policies. No records will be destroyed without the written 
consent of the sponsor, if applicable. It is the responsibility of the sponsor to inform the PI when 
these documents no longer need to be retained.  
 
14.3 PROTOCOL DEVIATIONS  
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or SOP 
requirements. The noncompliance may be either on the part of the participant, the investigator, or 
the study site staff. As a result of deviations, corrective actions are to be developed by the site and 
implemented promptly. These practices are consistent with ICH E6, sections: 
• 4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3. 
• 5.1 Quality Assurance and Quality Control, section 5.1.1. 
• 5.20 Noncompliance, sections 5.20.1 and 5.20.2. 
 
It is the responsibility of the study team to use continuous vigilance to identify and report 
deviations within 2 working days of identification of the protocol deviation, or within 2 working 
days of the scheduled protocol-required activity. All deviations must be addressed in study 
source documents, reported to PI Bryan and Co-I Camidge. Protocol deviations must be sent to 
the local IRB per their guidelines. The site PI/ study staff is responsible for knowing and 
adhering to their IRB requirements. Further details about the handling of protocol deviations will 
be included in the -SOP and/or study procedures manual.  
 
14.4 PUBLICATION AND DATA SHARING POLICY 
This study will comply with the NIH Public Access Policy, which ensures that the public has 
access to the published results of NIH-funded research. It requires scientists to submit final peer-
reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed Central 
upon acceptance for publication. 
 
The International Committee of Medical Journal Editors (ICMJE) member journals have adopted 
a clinical trials registration policy as a condition for publication. The ICMJE defines a clinical trial 
as any research project that prospectively assigns human participants to intervention or concurrent 
comparison or control groups to study the cause-and-effect relationship between a medical 
intervention and a health outcome. Medical interventions include drugs, surgical procedures, 
devices, behavioral treatments, process-of-care changes, and the like. Health outcomes include any 
biomedical or health-related measures obtained in patients or participants, including 
pharmacokinetic measures and adverse events. The ICMJE policy, and the Section 801 of the Food 
and Drug Administration Amendments Act of 2007 requires that all clinical trials be registered in 
a public trials registry such as ClinicalTrials.gov, which is sponsored by the National Library of 
Medicine. Other biomedical journals are considering adopting similar policies. For interventional 

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clinical trials performed under NIH IC grants and cooperative agreements, it is the grantee’s 
responsibility to register the trial in an acceptable registry, so the research results may be 
considered for publication in ICMJE member journals. The ICMJE does not review specific 
studies to determine whether registration is necessary; instead, the committee recommends that 
researchers who have questions about the need to register err on the side of registration or consult 
the editorial office of the journal in which they wish to publish. 
  
FDAAA mandates that a “responsible party” (i.e., the sponsor or designated PI) register and report 
results of certain “applicable clinical trials”. 
• Trials of Drugs and Biologics: Controlled, clinical investigations, other than Phase I 
investigations, of a product subject to FDA regulation; 
• Trials of Devices: Controlled trials with health outcomes of a product subject to FDA 
regulation (other than small feasibility studies) and pediatric postmarket surveillance 
studies. 
 
15 
STUDY ADMINISTRATION 
15.1 
STUDY LEADERSHIP 
The pilot study will be under the leadership of PI Bryan with assistance from Co-Is Camidge, 
Bowles, Bidwell, and Klawitter. 
 
16 
CONFLICT OF INTEREST POLICY 
Independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical. Any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed.by the 
University of Colorado Denver’s (UCD) Office of Regulatory Compliance Conflict of Interest and 
Commitment Management (COIC) program. Persons with a perceived conflict of interest will have 
such conflicts managed in a way that is appropriate to their participation in the trial. Conflict of 
Interest management plans are project-specific and are reviewed at least annually. UCD has 
integrated the institutional conflict of interest management program with its existing program. 
 
17  
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18  
APPENDICES  
This section is not applicable. 
 

PI:  Bryan 
Protocol #:  18-0836 
Version Date: May 31st, 2022 
 
 
47 of 47 
 
Version 
Date 
Significant Revisions  
1 
4/20/2018 
 
2 
5/22/2018 
Updates per PRMS review comments 
3 
6/8/2018 
Updated Statistical and Analytical Plan 
4 
8/27/2018 
COMRIB Requested Revisions 
5 
6/12/2019 
Eligibility edits for enrollment  
6 
6/30/2020 
Edits for remote visit descriptions and eliminating 
research blood draws due to COVID