A Study Investigating the Bioavailability of CBD and THC in an Emulsion Product in a Healthy Population
Condition: Healthy; Cannabis
MeSH terms: Marijuana Abuse
Study type: Interventional
Phase: Phase 1

Summary: 
      The objective of this study is to investigate the bioavailability of Cannabidiol (CBD) and
      Tetrahydrocannabinol (THC) in an emulsion product against a comparator product. Thirty-two
      participants will be randomized into a single-center, double-blind, parallel trial.
      Participants will be dosed in clinic and blood and urine samples will be taken over a 12-hour
      period. Blood and urine samples will also be collected for 48 hours post-dose at check-in
      visits. Questionnaires regarding drug effects and cognitive function will also be completed
      following each blood sampling. Participants who consumed the comparator product will be asked
      to return to the clinic following a wash-out period of at least 45 days to consume the
      emulsion product in-clinic and complete questionnaires at the same specified time points over
      a 12-hour period.
    

Detailed description: 
      The use of marijuana or cannabis for medicinal purposes is deeply rooted in history, and
      medicinal preparations from Cannabis indica and C. sativa have been used for almost 5,000
      years for treating nausea, inflammation, vomiting and pain. However, the major lipophilic
      cannabinoids out of >60 terpenophenolic compounds that cause these effects were not
      identified until the early 20th century. Sativex, dronabinol, and nabilone (synthetic or
      similar to cannabinoids) are the only currently approved cannabis derived medicinal products
      in the United States and Canada for different conditions such as nausea and vomiting
      associated with cancer, multiple sclerosis, intractable cancer pain, etc. Controversies
      regarding legal, medicinal and ethical use of cannabis have increasingly placed this plant in
      the spotlight in recent years. Although the use of cannabis fell from favor to fear in the
      early 1900s, a widespread support for its use for medicinal purposes has been on the rise in
      several countries across the world.

      Cannabidiol (CBD), a cannabinoid constituent of cannabis plants possesses anxiolytic,
      antipsychotic, antiemetic and anti-inflammatory properties, without exhibiting the
      psychoactive effects of Δ9-tetrahydrocannabinol (Δ9-THC), the other major cannabinoid from
      the same plant Δ9-THC and CBD are biosynthesized as Δ9-tetrahydrocannabinolic acid and
      cannabidiolic acid from the common precursor olivetol. Both Δ9-THC and CBD exert their
      effects by interacting with the G protein-coupled cannabinoid receptors (GPCRs), CB1 and CB2
      with varying affinities. While CB1 receptors are expressed in large quantities in the brain
      and regions central nervous system, and in lower amounts in peripheral tissues; the less
      studied CB2 receptors have been identified to be localized to immune cells, tonsils and the
      spleen. The CB1 receptors have been identified to play significant roles in pain perception,
      memory, motor regulation, appetite, mood, and sleep, whereas the CB2 receptors have been
      linked with anti-inflammation, pain reduction and reducing tissue damage. Physiologically,
      upon activation by the endocannabinoids like anandamide and 2-arachidonylglycerol (2-AG)
      (which are short lived), CB1 and CB2 trigger a downstream cascade of events that mediate
      homeostasis and healthy functioning. In contrast, the phytocannabinoids Δ9-THC and CBD that
      directly or indirectly interact with CB1 and CB2 with varying affinities modulate the
      activities of these receptors for prolonged durations.

      Δ9-THC is the major psychoactive cannabinoid and mimics the action of the endogenous
      cannabinoid receptor ligands anandamide and 2-AG by activating both CB1 and CB2 receptors.
      Due to its binding to CB1 receptors which are specifically present in the central nervous
      system in areas associated with pain (eg. Spinal trigeminal nucleus, amygdala, basal ganglia
      and periaqueductal gray), Δ9-THC possesses antinociceptive activity and is hence used as an
      analgesic agent in certain pain medications. In addition, Δ9-THC has also been shown to be
      effective in the treatment of glaucoma, nausea, chronic pain, multiple sclerosis, epilepsy
      and inflammation in several pre-clinical and clinical studies . However, Δ9-THC abuse is a
      global concern and due to the behavioural and psychological dependence, Δ9-THC has remained a
      subject of controversy and a largely unproved therapy with limited studies establishing its
      benefit-to-risk ratio, safety and efficacy for different indications.

      CBD, which is the non psychoactive phytocannabinoid, and can hence be a promising therapeutic
      has gained increasing attention in the recent past. Previous studies have shown that CBD is a
      promising potential therapeutic for various disorders of the central nervous system including
      anxiety, epilepsy, schizophrenia, Parkinson's disease, Alzhiemer's disease, multiple
      sclerosis and many more. Unlike Δ9-THC, CBD does not activate CB1 and CB2, and instead blocks
      the cannabinoids that activate these receptors by a complex mechanism. Several groups have
      proposed that this activity not only results in the non-psychotropic effects exhibited by CBD
      but may also account for ameliorating some of the psychotropic effects shown by Δ9-THC. In
      addition, by lowering the psychoactivity of Δ9-THC, CBD may also potentiate some of Δ9-THC's
      benefits by enhancing its tolerability and widening its therapeutic window. CBD can also
      inhibit or delay the reuptake and hydrolysis of the endocannabinoids like anandamide and
      adenosine. CBD has also been hypothesized to interact with several other non-endocannabinoid
      signaling systems such as serotonin receptors, vanilloid receptors, GPR-55 (orphan
      receptors), peroxisome proliferator activated receptors (PPARs) making it a "multi-target
      drug". In addition to these activities, the polyphenolic ring in CBD also results in it being
      a potent antioxidant. All these results have prompted the exploration of the therapeutic
      potential of CBD for a range of neuropsychiatric as well as inflammatory disorders.

      Several groups have attempted to study the pharmacokinetics and pharmacodynamics of CBD and
      Δ9-THC. It is generally accepted in drug research that lipophilicity promotes the passage of
      molecules across cellular barriers and therefore the most lipophilic compounds will have
      greatest intestinal absorption. Due to the lipophilicity of cannabinoids, smoking results in
      the fastest absorption of CBD and Δ9-THC, however, the half-life of CBD in humans was found
      to be between 18-33 h upon intravenous injection, 27-35 h upon smoking, and 2-5 days upon
      oral administration. Bioavailability of oral and smoked CBD in humans was found to be around
      6% and 31%, respectively; and bioavailability of oral and smoked Δ9-THC is shown to be 4-12%
      and 10-27% respectively. Other studies have previously determined the time to achieve peak
      plasma concentration (tmax) as 1.5- 4 h for different doses of CBD and 1-2 h for different
      doses of Δ9-THC. This single-center, randomized, double-blind, comparator-controlled,
      parallel study will investigate the bioavailability of CBD and Δ9-THC in the test product-
      SolutechTM - TC10 manufactured by New Age Ventures LLC in a healthy population.
    

Intervention name(s): Cannabis Preparation; Cannabis Preparation
Intervention type(s): Drug; Drug
Intervention description(s): Dosed as a single oral dose; Dosed as a single oral dose
Other intervention name(s): Cannabis emulsion; Cannabis oil
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, double-blind, comparator-controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Cannabis; THC; CBD; Healthy Adult