A Study Investigating the Bioavailability of CBD and THC in an Emulsion Product in a Healthy Population

Healthy Clinical Trial

Official title: A Single-center, Randomized, Double-blind, Comparator-controlled Parallel Study Investigating the Bioavailability of Cannabidiol and Δ9-Tetrahydrocannabinol in an Emulsion Product in a Healthy Population

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Cannabis
• Healthy
• Marijuana Abuse

• NCT number: NCT04601207
• Study type: Interventional
• Source: New Age Ventures LLC
• Status: Completed
• Phase: Phase 1
• Start date: June 19, 2020
• Completion date: November 30, 2020