CBD Showed Very Low Abuse Potential Even at Extremely High Doses | Research

The takeaway

In a rigorous abuse potential study with polydrug users, therapeutic doses of CBD (750 mg) showed significantly low abuse potential, and even supratherapeutic doses (4500 mg) produced effects far below those of alprazolam and dronabinol.

Regulators, CBD consumers, medical professionals prescribing CBD products.

CBD drug-liking at all doses was significantly lower than both alprazolam and dronabinol (P less than or equal to 0.004), with no cognitive impairment at any dose.

What the researchers found

Therapeutic CBD (750 mg) showed significantly low abuse potential. High doses (1500 mg, 4500 mg) had detectable subjective effects compared to placebo but were significantly lower than alprazolam and dronabinol on drug-liking, overall-liking, and take-drug-again measures (all P values 0.004 or less). CBD did not impair cognitive or psychomotor function at any dose.

Why it matters

This study was critical for CBD's regulatory pathway. By demonstrating low abuse potential in a population most sensitive to detecting drug effects, it supported the argument that CBD should not be heavily restricted, paving the way for more accessible medical use.

The numbers in context

43 subjects dosed, 35 in pharmacodynamic analysis. CBD at 750 mg showed no significant drug-liking versus placebo. Even at 4500 mg (6x therapeutic dose), CBD drug-liking was significantly lower than both active controls.

How the study worked

Single-dose, randomized, double-blind, double-dummy, placebo- and active-controlled crossover trial in 43 healthy recreational polydrug users. CBD (750, 1500, 4500 mg) was compared with alprazolam (2 mg), dronabinol (10 mg, 30 mg), and placebo.

What this study cannot tell us

Single-dose study does not assess abuse potential of chronic use. Polydrug user population is specific. Very high doses (4500 mg) are unlikely to be used clinically. The oral solution formulation may differ from other CBD products.

How to read the evidence

Strong - gold-standard abuse potential study design (randomized, double-blind, active- and placebo-controlled crossover) in the appropriate population.

When this study was published

Published in 2018. CBD has since been rescheduled based partly on these findings.

The bigger picture

This study was part of the regulatory submission for Epidiolex (CBD for epilepsy). Its findings that CBD has minimal abuse potential - even in drug-experienced users at extreme doses - distinguish it fundamentally from THC-containing cannabis products.

Questions still open

Should CBD be scheduled differently from THC given these findings? Do other CBD formulations (vaping, smoking) have different abuse potential? Would results differ in cannabis-naive versus experienced populations?

Common questions

Is CBD addictive?

This study found CBD has very low abuse potential. Even at 6 times the therapeutic dose (4500 mg), drug-experienced polydrug users rated CBD significantly lower than alprazolam and dronabinol on all measures of drug-liking and desire to take again.

Does CBD get you high?

At therapeutic doses (750 mg), CBD was not distinguishable from placebo on drug-liking measures. Very high doses produced detectable effects, but these were significantly smaller than those of alprazolam (a benzodiazepine) or dronabinol (oral THC).

Read the original research

Abuse potential assessment of cannabidiol (CBD) in recreational polydrug users: A randomized, double-blind, controlled trial.

Epilepsy & behavior : E&B, 88, 162-171

View on PubMed ↗Publisher’s paper ↗

Citation

Schoedel, Kerri A; Szeto, Isabella; Setnik, Beatrice; Sellers, Edward M; Levy-Cooperman, Naama; Mills, Catherine; Etges, Tilden; Sommerville, Kenneth. (2018). Abuse potential assessment of cannabidiol (CBD) in recreational polydrug users: A randomized, double-blind, controlled trial.. Epilepsy & behavior : E&B, 88, 162-171. https://doi.org/10.1016/j.yebeh.2018.07.027