Study on Regulated Cannabis Sales in Pharmacies

Study Overview
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Brief Summary
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Though regulated cannabis sales are increasing, little is known about the individual health effects of cannabis regulation. Data from countries with a regulated market can be used to test the effect of regulation on the price of cannabis in the illicit market, and to explore its effect on social and health outcomes at the societal level, but strength of evidence for individual health and social outcomes is more limited because it must be aggregated on a state or country level. Data on individual and social outcomes should include baseline measurements before and outcome measurements after regulations changed. In this context, randomized-controlled trials are the least biased source of data on the effects of interventions. The SCRIPT study aims to investigate the individual health and social impact on recreational cannabis users who are allowed to purchase authorized, regulated cannabis from Swiss pharmacies compared to users who buy cannabis on the illicit market. Participants are randomly allocated in one of the two groups and followed-up for 6 months. After 6 months, all participants are allowed to participate in the intervention and the cohort is followed up for another 18 months. The intervention includes various offers: Participants can choose between cannabis sorts and delivery methods, and they are encouraged to shift from smoking cannabis to vaping cannabis-containing e-liquids, vaporizing cannabis blossoms or using oral cannabis. Vaping / vaporizing electronic devices are also recommended. At the same time, pharmacists offer opportunistic smoking cessation and problematic cannabis, alcohol use and further drug use counseling that conforms to motivational interviewing principles. The SCRIPT study adheres to rigorous quality criteria for the production and storage of regulated cannabis products. Only vaping / vaporizing electronic devices which are validated to reduce exposure to toxicants compared to cannabis smoking are recommended.

Detailed Description
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Cannabis is the most consumed illegal substance in Switzerland. Many countries and an increasing number of US states have regularized cannabis production and distribution for non-medical use. Analyses of the effects of regulation are promising on a population level, but the causal effects of regulation have only been assessed in before-after studies or ecological comparisons between countries or states. Randomized controlled trials (RCT) are needed to better assess the effects of cannabis regulation on individuals. Since May 2021, the conduct of scientific pilot studies are allowed in Switzerland. While rigorous quality and safety standards cannot be implemented in illicit production and distribution networks, they can be implemented in regulated markets. Beyond psychiatric outcomes, the major hazard associated with cannabis use on somatic health outcomes are mostly related to smoking cannabis and mixing it with tobacco. Regulation therefore also opens the door to harm reduction strategies like counseling users to vape, vaporize, or eat cannabis instead of smoking it. Regulated sale in pharmacies would further facilitate smoking cessation counseling and access to health and social care for those in need. The SCRIPT trial aims to investigate the individual health and social impact on recreational cannabis users who are offered a multimodal intervention of authorized, regulated cannabis sale in combination with counselling on reducing harm (intervention group) compared to users who continue to buy cannabis on the illicit market (control group). The intervention group is allowed to purchase regulated cannabis in authorized pharmacies. The intervention includes various offers: Participants can choose between cannabis sorts and delivery methods, and they are encouraged to shift from smoking cannabis to vaping cannabis-containing e-liquids, vaporizing cannabis blossoms or using oral cannabis. Vaping / vaporizing electronic devices are also recommended. At the same time, pharmacists offer opportunistic smoking cessation and problematic cannabis, alcohol use and further drug use counseling that conforms to motivational interviewing principles. The control group receives no intervention and is expected to continue purchasing cannabis from the illicit market. This is a multicenter, pragmatic, open-labelled randomized controlled trial from baseline to 6-months follow-up. After 6 months, the control group is allowed to purchase cannabis in pharmacies, too, and the study designs changes to a cohort-study.

Official Title
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The Safer Cannabis - Research In Pharmacies Randomized Controlled Trial (SCRIPT)

Conditions
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Marijuana Smoking, Cannabis, Cannabis Use

Intervention / Treatment
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* Drug: Regulated cannabis from authorized pharmacies
* Drug: Cannabis from the illicit market


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years old (validated with valid identification document) Written informed consent Regular cannabis user: Self-reported cannabis use at least once a month over the last 6 months and verified cannabis exposure based on urine analysis at baseline Resident status in the canton of Bern (for cannabis purchase in the cities of Bern or Biel) or in the city of Lucerne (for cannabis purchase in the city of Lucerne) (validated with registration confirmation from the municipality or confirmation of the residential address) Exclusion Criteria: Pregnant women (pregnancy test based on urine sample) Breastfeeding women (self-reported) People with a prescription for medical cannabis (self-reported) People currently in psychiatric inpatient treatment (self-reported) People with current, severe psychosis (self-reported and confirmed by study nurse/study physician) People with current, severe suicidal thoughts (self-reported and confirmed by study nurse/study physician) Inability to follow the procedures of the study due to severe cognitive impairment or language problems People who cannot attend the baseline study visit in-person People planning to move out of the canton of residence within 6 months of entering the trial. People who are participating or have participated (inclusion date up to one year ago) in another cannabis pilot trial which allows to buy regulated cannabis (validated by matching untraceable codes between studies witch the same catchment area).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a multicenter, pragmatic, open-labelled randomized controlled trial from baseline to 6-months follow-up. After 6 months, the control group is allowed to purchase cannabis in pharmacies, too, and the study design changes to a cohort-study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regulated cannabis from authorized pharmacies (intervention group)<br>Multimodal intervention of authorized, regulated cannabis sale in combination with counselling on reducing harms for recreational cannabis users in Swiss pharmacies (intervention group). | Drug: Regulated cannabis from authorized pharmacies<br>* The intervention group is allowed to purchase regulated cannabis in authorized pharmacies. The intervention includes various offers: Participants can choose between cannabis sorts and delivery methods, and they are encouraged to shift from smoking cannabis to vaping cannabis-containing e-liquids, vaporizing cannabis blossoms or using oral cannabis. Vaping / vaporizing electronic devices are also recommended. At the same time, pharmacists offer opportunistic smoking cessation and problematic cannabis, alcohol use and further drug use counseling that conforms to motivational interviewing principles. Study participants can choose between different cannabis-containing products such as dried cannabis flowers, cannabis concentrates (colloquially called hashish or hash), e-liquids and oral cannabis. Besides the cannabis products, participants can buy vaping or vaporizing electronic devices at the pharmacy (they are not considered as study products).<br>|
| Active Comparator: Cannabis from the illicit market (control group)<br>The control group receives no intervention and is expected to continue purchasing cannabis from the illicit market. | Drug: Cannabis from the illicit market<br>* The control group receives no intervention and is expected to continue purchasing cannabis from the illicit market.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with self-reported shift from smoking cannabis to safer alternative delivery methods of cannabis and, if applicable, shift from smoking tobacco to alternate nicotine delivery method or nicotine cessation | Self-reported shift from smoking cannabis to safer alternative delivery methods of cannabis and, if applicable, shift from smoking tobacco to alternate nicotine delivery method or nicotine cessation, validated by carbon monoxide (CO) in exhaled air. To distinguish between non-smoker and smoker, the cut-off for the CO measurement is <10 parts per million (ppm) and no self-reported use within the last 7 days (7-day point prevalence of abstinence). The validation is based on the worst-case principle. Smokers are considered as Participants with a positive CO measurement, even if the self-report is negative. Participants with a positive self-declaration, even if the CO measurement is negative. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-reported delivery method of cannabis and, if applicable, of other tobacco/nicotine products | Based on interviews by phone or online | 12, 18, & 24 months | 
| Concentration of toxicants in urine | Measured in urine from a sub-sample | 6 months | 
| Type of cannabis sold per participant in pharmacies |  | 6, 12, 18, & 24 months | 
| Amount of cannabis sold per participant in pharmacies |  | 6, 12, 18, & 24 months | 
| Self-reported cannabis purchase on the illicit market |  | 6, 12, 18, & 24 months | 
| Self-reported frequency of use |  | 6, 12, 18, & 24 months | 
| Concentration of THC and CBD in cannabis bought on the illicit market | Measured in cannabis from a random sub-sample. | 6 months | 
| Concentration of contaminants in cannabis bought on the illicit market | Measured in cannabis from a random sub-sample. | 6 months | 
| Severity of generalised anxiety disorder | Recorded as participant-reported outcome. Measured by Generalised Anxiety Disorder (GAD-7) questionnaire (scores range from 0 to 21, with higher scores indicating higher levels of generalised anxiety) | 6, 12, 18, & 24 months | 
| Attention Deficit Hyperactivity Disorder (ADHD) symptoms in adults | Recorded as participant-reported outcome. Measured by Adult ADHD Self-Report Scale (ASRS) questionnaire. | 6, 12, 18, & 24 months | 
| Severity of depression | Recorded as participant-reported outcome. Measured by the Patient Health Questionnaire-9 (PHQ-9) (scores range from 0 to 27, with higher scores indicating more depressive symptoms) | 6, 12, 18, & 24 months | 
| Number of psychotic symptoms | Recorded as participant-reported outcome. Measured by the Psychotic Symptoms (PS) Checklist | 6, 12, 18, & 24 months | 
| Somatic health | Recorded as participant-reported outcome. Measured by Pittsburgh Sleep Quality Index (PSQ-I) questionnaire. | 6, 12, 18, & 24 months | 
| Impact of COPD | Recorded as participant-reported outcome. Measured by COPD Assessment Test (CAT) questionnaire (scores range from 0 to 40, with higher scores indicating indicating a more severe impact of COPD on a patient's life). | 6, 12, 18, & 24 months | 
| Severity of dyspnea | Recorded as participant-reported outcome. Measured by Modified Medical Research Council (MMRC) scale for dyspnea. | 6, 12, 18, & 24 months | 
| COPD exacerbation assessment | Recorded as participant-reported outcome. | 6, 12, 18, & 24 months | 
| Quality of life (health-related) | Recorded as participant-reported outcome. Measured by the European Quality of Life-5 Dimensions (EQ-5D) questionnaire. | 6, 12, 18, & 24 months | 
| Perception of stress | Recorded as participant-reported outcome. Measured by the Perceived Stress Scale (PSS). | 6, 12, 18, & 24 months | 
| Cannabis use and purchase behavior | Recorded as participant-reported outcome. | 6, 12, 18, & 24 months | 
| Cannabis use disorder | Recorded as participant-reported outcome. Measured by Cannabis Use Disorders Identification Test - Revised (CUDIT-R) questionnaire. | 6, 12, 18, & 24 months | 
| Consumption motives | Recorded as participant-reported outcome. | 6, 12, 18, & 24 months | 
| Consumption competence | Recorded as participant-reported outcome. | 6, 12, 18, & 24 months | 
| Consumption risk perception | Recorded as participant-reported outcome. | 6, 12, 18, & 24 months | 
| Nicotine/tobacco use behavior | Recorded as participant-reported outcome | 6, 12, 18, & 24 months | 
| Exposure to second-hand smoke | Recorded as participant-reported outcome | 6, 12, 18, & 24 months | 
| Exposure to environmental pollution | Recorded as participant-reported outcome | 6, 12, 18, & 24 months | 
| Alcohol consumption behavior | Recorded as participant-reported outcome. Measured by Alcohol Use Disorders Identification Test (AUDIT-C). | 6, 12, 18, & 24 months | 
| Drug consumption behavior | Recorded as participant-reported outcome. Measured by Alcohol, Smoking and Substance Involvement Screening Test (ASSIST V3.0). | 6, 12, 18, & 24 months | 
| Medication use behavior | Recorded as participant-reported outcome | 6, 12, 18, & 24 months | 
| Treatment/Counseling Experience | Recorded as participant-reported outcome | 6, 12, 18, & 24 months | 
| Use of health and social services | Recorded as participant-reported outcome. | 6, 12, 18, & 24 months | 
| Body mass index | Cardiovascular risk factor (CVRF) measured at physical examinations. | 6 months | 
| Blood pressure | Cardiovascular risk factor (CVRF) measured at physical examinations. | 6 months | 
| Waist-to-hip ratio | Cardiovascular risk factor (CVRF) measured at physical examinations. | 6 months | 
| Number of safety events | Recorded as participant-reported outcome. | 6, 12, 18, & 24 months | 
| Inflammation-related protein biomarkers | Measured from blood samples from a sub-sample. Analysis of 92 protein biomarkers associated with inflammatory and immune response processes using the Olink® Target 96 Inflammation Panels. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cannabis, Cannabis Use, Cannabis sativa, Cannabinoids