A two-site inpatient RCT in treatment-seeking adult patients with CUD receiving 6 days of nabiximols or placebo with concomitant MI/CBT during a 9-day admission, found that nabiximols reduced withdrawal and improved treatment retention , but did not reduce cannabis use, dependence or cannabis-related problems compared to placebo . Nabiximols was not associated with greater intoxication or adverse events. A pilot, outpatient RCT in treatment seeking cannabis dependent adults receiving 12-week treatment with self-titrated nabiximols use or placebo, concurrent with weekly MI and CBT, found that nabiximols was well tolerated with no serious adverse events, but had no effect on withdrawal symptoms, cannabis use and abstinence, compared to placebo. In contrast, a multi-site, outpatient RCT in cannabis dependent adults receiving 12-week treatment with self-titrated nabiximols use or placebo, concurrent with 6 sessions of CBT, found that nabiximols was well tolerated with few adverse events, had no effect on withdrawal symptoms, cannabis grow facility craving and cannabis-related problems, but reduced cannabis use during the trial, compared with placebo.
The reduction in cannabis use in the nabiximols group, compared to placebo, was maintained 12 weeks after treatment . To summarize, the evidence from placebo-controlled laboratory studies suggests that treatment with dronabinol dose-dependently decrease withdrawal symptoms, with some evidence that higher doses produce cannabis intoxication and drug liking. Evidence from large placebo-controlled RCTs in cannabis dependent adults combining dronabinol with MI over 11-12 weeks partly supports this: 40 mg/day reduced withdrawal symptoms and improved treatment retention, but not cannabis use and abstinence , but a higher dose, 60 mg/day combined with lofexidine had no effect on neither withdrawal symptoms nor abstinence or treatment retention . Nabilone has been less examined, but the evidence from placebo-controlled studies is similar: a laboratory study suggests that 6 or 8 mg/day reduces withdrawal symptoms , and a small RCT in cannabis dependent adults found no effect on cannabis use. Evidence from placebo-controlled studies of nabiximols combined with MI and CBT is more mixed: out of the three conducted RCTs in cannabis dependent adults, self-titrated nabiximols reduced withdrawal symptoms, but had no effect on cannabis use, dependence or cannabis-related problems in one study; had no effect on neither withdrawal symptoms nor cannabis use or abstinence in another study with a higher dose; and had no effect on withdrawal symptoms, craving and cannabis-realted problems, but reduced cannabis use in a large study.
Recently, studies have also examined the effect of FAAH inhibitors or CBD in adults with CUD . FAAH forms a part of the endo-cannabinoid system by breaking down endo-cannabinoids such as anandamide. By inhibiting this breakdown process, cannabis grow system FAAH inhibitors increase endo-cannabinoid levels, which may represent a therapeutic mechanism for the treatment of CUD. Preclinical research has shown that FAAH inhibitors can attenuate cannabis withdrawal symptoms in THC-dependent mice . So far, only one RCT has examined the effects of FAAH inhibitor treatment on cannabis use and cannabis pathology in humans . In a double-blind, place-controlled, parallel group phase 2a trial in adults with cannabis dependence, participants received 4 mg daily PF-04457845 or placebo during 4 weeks. Relative to placebo, treatment with PF-04457845 reduced symptoms of cannabis withdrawal, and self-reported cannabis use at 4 weeks, which was confirmed by lower urinary THC-COOH concentrations.
Further, there was no difference between reported adverse events and retention in the two groups. For example, preclinical studies show that CBD attenuates drug-seeking behavior , and a study found that CBD reversed the reinforcing effects of cannabis in youth , supporting CUD treatment potential. The multiple receptor mechanisms of CBD outlined earlier are believed to form the neurobiological underpinnings of the effects of CBD on the regulation of reinforcing, motivational and withdrawal-related effects as documented in preclinical and clinical studies . It is still not known precisely how CBD interacts with the dopaminergic system to modify the motivational effects of psychoactive drugs, but available data suggest a role for CBD in regulating the activity of the mesolimbic dopaminergic system . This role has been emphasized by the localization of cannabinoid receptors in the mesolimbic circuit orchestrating the synthesis and release of dopamine .