The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users

Abstract

BACKGROUND Prior studies have separately examined the effects of dronabinol (oral THC) on cannabis withdrawal, cognitive performance, and the acute effects of smoked cannabis. A single study examining these clinically relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders. METHODS Thirteen daily cannabis smokers completed a within-subject crossover study and received 0, 30, 60 and 120 mg dronabinol per day for 5 consecutive days. Vital signs and subjective ratings of cannabis withdrawal, craving and sleep were obtained daily; outcomes under active dose conditions were compared to those obtained under placebo dosing. On the 5th day of medication maintenance, participants completed a comprehensive cognitive performance battery and then smoked 5 puffs of cannabis for subjective effects evaluation. Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad-libitum cannabis use. RESULTS Dronabinol dose-dependently attenuated cannabis withdrawal and resulted in few adverse side effects or decrements in cognitive performance. Surprisingly, dronabinol did not alter the subjective effects of smoked cannabis, but cannabis-induced increases in heart rate were attenuated by the 60 and 120 mg doses. CONCLUSIONS Dronabinol’s ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use. The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120mg per day. Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment, using an expanded range of doses, is warranted.

Acute and Chronic Effects of Cannabinoids on Human Cognition—A Systematic Review

“…Whether working memory is impaired by cannabis is less clear, possibly because of the wide range of different working memory tasks employed. Acute administration of THC, dronabinol, or nabilone affected working memory inconsistently across Sternberg, delayed matching to sample, spatial or numeric working memory, n-back, digit recall, and digit span tasks (36)(37)(38)(39)(40)42,43,(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78). Similarly, chronic cannabis use was shown to impair working memory in young adults on immediate recall (79), verbal reasoning (80), and verbal n-back (81) working memory tasks, but not on spatial working memory (48,82) or digit span (52,53), whereas spatial working memory was impaired in adolescent users (46), suggestive of differential effects in the developing brain.…”

“…In heavy users, high-dose smoked cannabis resulted in more collisions in a virtual maze task (106) but did not affect critical tracking (89,90). Oral administration of THC [or IV (37)], nabilone, or dronabinol impaired psychomotor function in seven of eight studies (37,43,68,74,76,77,107), with only one study finding no significant impairment (73). Findings regarding the chronic effects of cannabis on psychomotor function are mixed, being reported as impaired (51,54,80,108), improved (48), and unaffected (46,78).…”

Δ9-Tetrahydrocannabinol and Endocannabinoid Degradative Enzyme Inhibitors Attenuate Intracranial Self-Stimulation in Mice

“…cannabinoids (albeit in trace amounts in most cases), as well as other chemicals that could contribute to its subjective effects and abuse potential in humans. Moreover, pure THC is not typically used for recreational purposes by humans and can elicit aversive effects (Calhoun et al, 1998) or only modest reinforcing effects in experienced marijuana users (Hart et al, 2005;Vandrey et al, 2013). In light of these studies, the rightward shift in the frequency-rate curves of ICSS produced by subcutaneous injection of THC may accurately represent a low abuse liability in humans.…”

Impact of marijuana use on self-rated cognition in young adult men and women

“…One of the study strengths is that approximately half of the study participants in this study were female. Many previous studies on the effect of MJ on cognition have either not included women 23,24 or included fewer women than men [25][26][27][28][29][30] .…”