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All active drug treatments induced significantly more anxiety compared to placebo. After 15 mg oral THC, the concentration of THC in plasma was observed to have a weak, but statistically significant, positive correlation with systolic and diastolic blood pressure, "good drug effect", and "high". After high-dose oro-mucosal nabiximols, positive correlations were also observed between plasma THC concentrations and "anxious", "good drug effect", "high", "stimulated", and M-scale (marijuana-scale) scores.

A statistically significant increase in heart rate relative to placebo was observed after high-dose oral THC (15 mg Δ9-THC) and high-dose oro-mucosal nabiximols (16.2 mg Δ9-THC and 15 mg CBD), but the authors indicated that the increases appeared to be less clinically significant than those typically seen with smoked cannabis. A subjective feeling of a "high" was reported to be significantly greater after 15 mg oral THC compared to placebo and to 5 mg oral THC. In contrast, neither the high nor the low doses of oro-mucosal nabiximols were reported to produce a statistically significant subjective "high" feeling. Study subjects reported being most "anxious" approximately 4 h after administration of 5 mg oral THC, 3 h after 15 mg oral THC, 5.5 h after low-dose nabiximols, and 4.5 h after high-dose oro-mucosal nabiximols.

Consistent with other studies, the authors of this study reported that linear correlations between plasma THC concentrations and physiological or subjective effects were weak. Lastly, although CBD did not appear to significantly modulate the effects of THC, the authors suggested it might have attenuated the degree of the subjective "high".

Anecdotal information and findings from some animal studies suggest that cannabinoids (e.g. THC) might be useful in treating the symptoms associated with opioid withdrawalReference 843Reference 1075-Reference 1078, but there are no supporting clinical studies of efficacy in this regard. One literature review suggests that under certain circumstances, cannabis use can be associated with positive treatment prognosis among opioid-dependent cohortsReference 1066. Cannabis abuse and dependence were predictive of decreased heroin and cocaine use during treatment, and intermittent use of cannabis was hemp oil associated with a lower percentage of positive opioid urine drug screens and improved medication compliance on naltrexone therapyReference 1066. A few qualitative studies have found that people who use heroin report that they are able to reduce their heroin use by using cannabisReference 1079Reference 1080. In one study looking at people who inject drugs (PWID), smoking cannabis was reported to reduce anxiety and craving experienced while transitioning away from daily heroin useReference 1079, while in another study, medical cannabis patients reported using cannabis to substitute or wean off prescription opioidsReference 1080.

Another study found that street-recruited PWIDs who reported using cannabis used opioids (i.e. heroin) less frequentlyReference 1081. However, a study that investigated the use of smoked cannabis to alleviate symptoms of opioid withdrawal did not appear to find any effect of cannabis use on opioid-withdrawal symptomsReference 1082. In this study, 116 outpatient heroin and cocaine users (of whom 46 were also cannabis users) participating in a 10-week methadone-taper phase of a randomized clinical trial were assessed for self-rated opioid withdrawal symptoms. The study found that opioid withdrawal scores did not differ between users and non-cannabis users suggesting that smoked cannabis did not reduce opioid withdrawal symptoms in this patient population.

The subjective and physiological effects after controlled administration of oro-mucosal nabiximols (Sativex®) or oral Δ9-THC have also been comparedReference 122. Increases in systolic blood pressure occurred with low (5 mg) and high (15 mg) oral doses of THC, as well as low (5.4 mg Δ9-THC and 5 mg CBD) and high (16.2 mg Δ9-THC and 15 mg CBD) oro-mucosal doses of nabiximols, with the effect peaking at around 3 h after administration. In contrast, diastolic blood pressure decreased between 4 and 8 h after dosing.

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