Abstract As countries adopt more permissive cannabis policies, it is increasingly important to identify strategies that can reduce the harmful effects of cannabis use. This study aimed to determine if increasing the CBD content of cannabis can reduce its harmful effects. Forty-six healthy, infrequent cannabis users participated in a double-blind, within-subject, randomised trial of cannabis preparations varying in CBD content. There was an initial baseline visit followed by four drug administration visits, in which participants inhaled vaporised cannabis containing 10 mg THC and either 0 mg (0:1 CBD:THC), 10 mg (1:1), 20 mg (2:1), or 30 mg (3:1) CBD, in a randomised, counter-balanced order. The primary outcome was change...

Please use this link to access this publication: https://www.nature.com/articles/s41380-023-02185-x Abstract A major public health concern of cannabis legalization is that it may result in an increase in psychotic disorders. We examined changes in emergency department (ED) visits for cannabis-induced psychosis following the legalization and subsequent commercialization (removal of restrictions on retail stores and product types) of non-medical cannabis in Ontario, Canada (population of 14.3 million). We used health administrative data containing the cause of all ED visits to examine changes over three periods; 1) pre-legalization (January 2014–September 2018); 2) legalization with restrictions (October 2018 – February 2020); and 3) commercialization (March 2020 – September 2021)....

Please use this link to access this publication: https://www.nature.com/articles/s41380-023-02148-2 Abstract Leveraging ~10 years of prospective longitudinal data on 704 participants, we examined the effects of adolescent versus young adult cannabis initiation on MRI-assessed cortical thickness development and behavior. Data were obtained from the IMAGEN study conducted across eight European sites. We identified IMAGEN participants who reported being cannabis-naïve at baseline and had data available at baseline, 5-year, and 9-year follow-up visits. Cannabis use was assessed with the European School Survey Project on Alcohol and Drugs. T1-weighted MR images were processed through the CIVET pipeline. Cannabis initiation occurring during adolescence (14–19 years) and young adulthood (19–22...

Abstract Cannabidiol (CBD), a constituent of cannabis with few psychoactive effects, has been reported in some studies to attenuate certain aspects of Δ(9)-tetrahydrocannabinol (THC) intoxication. However, most studies have tested only one dose of CBD in combination with one dose of oral THC, making it difficult to assess the nature of this interaction. Further, the effect of oral CBD on smoked cannabis administration is unknown. The objective of this multi-site, randomized, double-blind, within-subject laboratory study was to assess the influence of CBD (0, 200, 400, 800 mg, p.o.) pretreatment on the reinforcing, subjective, cognitive, and physiological effects of smoked cannabis (0.01 (inactive), 5.30-5.80% THC)....

Please use this link to access this publication. Abstract Rationale: The rationale of this study was to assess occurrence of withdrawal symptoms induced by abrupt cessation of cannabidiol (CBD) after prolonged administration in healthy volunteers. Methods: Thirty volunteers were randomized to receive 750 mg of a plant-derived pharmaceutical formulation of highly purified CBD in oral solution (100 mg/mL; Epidiolex® in the United States and Epidyolex® in Europe) twice daily (b.i.d.) for 4 weeks (Part 1) followed by 2 weeks of 750 mg b.i.d. CBD (Part 2, Arm 1) or matched placebo (Part 2, Arm 2). All volunteers completed the Cannabis Withdrawal Scale (CWS) and the 20-item...

Abstract Background Cannabidiol (CBD) is a naturally occurring constituent of the marijuana plant. In the past few years, there has been great interest in the therapeutic effects of isolated CBD and it is currently being explored for numerous disease conditions (e.g., pain, epilepsy, cancer, various drug dependencies). However, CBD remains a Schedule I drug on the U.S. Controlled Substances Act (CSA). Despite its status, there are no well-controlled data available regarding its abuse liability. Methods Healthy, frequent marijuana users (n=31) were enrolled in this within subject, randomized, placebo-controlled, double-blind, multisite study that administered oral cannabidiol (0, 200, 400, 800 mg) alone and in combination...

Please follow this link to access this publication: https://psycnet.apa.org/record/2003-05990-008 Abstract Withdrawal symptoms following cessation of heavy cannabis (marijuana) use have been reported, yet their time course and clinical importance have not been established. A 50-day outpatient study assessed 18 marijuana users during a 5-day smoking-as-usual phase followed by a 45-day abstinence phase. Parallel assessment of 12 ex-users was obtained. A withdrawal pattern was observed for aggression, anger, anxiety, decreased appetite, decreased body weight, irritability, restlessness, shakiness, sleep problems, and stomach pain. Onset typically occurred between Days 1-3, peak effects between Days 2-6, and most effects lasted 4-14 days. The magnitude and time course of these...

Abstract Background: A formal single ascending and multiple dose pharmacokinetic (PK) trial of cannabidiol (CBD) oral solution was required to determine the safety and tolerability of CBD, the maximum tolerated dose, and to examine the effect of food on CBD PK parameters. Objective: This trial assessed the safety, tolerability and PK of CBD oral solution in healthy adult volunteers, as well as the effect of food on CBD PK parameters. Methods: The study consisted of three arms: single ascending dose (1500, 3000, 4500 or 6000 mg CBD [n = 6 per group]/placebo [n = 8; 2 per CBD dose group]), multiple dose (750 or 1500 mg CBD...

Abstract Rationale: Treatment with a highly purified oral solution of cannabidiol (CBD), derived from the plant Cannabis sativa L., demonstrated some evidence of central nervous system (CNS)-related adverse events in patients enrolled in phase 3 trials for treatment of childhood-onset epilepsy. Cannabidiol was categorized as a Schedule 1 substance by the United States Drug Enforcement Administration; therefore, it was important to test CBD for human abuse potential. Methods: This was a single-dose, randomized, double-blind, double-dummy, placebo- and active-controlled crossover trial. The abuse potential of single oral doses of plant-derived pharmaceutical formulations of highly purified CBD (Epidiolex®; 750 mg, 1500 mg, and 4500 mg) was compared with...

Abstract Due to a lack of published pharmacokinetic (PK) and/or pharmacodynamic (PD) data, decision- making surrounding appropriate dosing of cannabis used for medical purposes is limited. This multiple-dose study evaluated the safety, tolerability, PK and PD of Spectrum Yellow oil [20 mg/mL cannabidiol (CBD)/<1mg/mL ∆9-tetrahydrocannabinol (THC)]. Participants (n=43) were randomized to one of five groups: 120 mg CBD and 5.4 mg THC daily, 240 mg CBD and 10.8 mg THC daily, 360 mg CBD and 16.2 mg THC daily, 480 mg CBD and 21.6 mg THC daily or placebo. Study medication was administered every 12 h for 7 consecutive days. Treatment-emergent adverse events (TEAEs);...