The safety of modafinil in combination with oral ∆9-tetrahydrocannabinol in humans

Abstract

Marijuana (cannabis) is the most widely used illicit substance globally, and cannabis use is associated with a range of adverse consequences. Currently, no medications have been proven to be effective for the treatment of cannabis addiction. The goals of this study were to examine the safety and efficacy of a potential treatment medication, modafinil, in combination with oral ∆9-tetrahydrocannabinol (THC). Twelve male and female occasional cannabis users participated in an outpatient double-blind, placebo-controlled, crossover study. Across four sessions, participants were randomly assigned to a sequence of four oral treatments: (1) 400 mg modafinil+placebo, (2) 15 mg THC+placebo, (3) 400 mg modafinil+15 mg THC, or (4) placebo+placebo. Outcome measures included heart rate, blood pressure, performance on the Rapid Visual Information Processing (RVIP), and the Hopkins Verbal Learning Test (HVLT), and subjective measures. Oral THC increased heart rate, and produced increased subjective ratings of feeling "high" and "sedated," as well as increased ratings of euphoria. Modafinil alone increased the Profiles of Mood States (POMS) subscales of vigor and tension. These findings support the safety of modafinil in combination with THC. The effects of modafinil in combination with a range of doses of THC need to be determined in future studies.

Fig. 1

Heart rate (a), systolic (b), and diastolic blood pressure (c) responses under 15 mg active THC plus 400 mg active modafinil (THC+MOD), 15 mg active THC plus placebo (THC+PLA), placebo plus 400 mg active modafinil (PLA+MOD), or placebo plus placebo (PLA+PLA) conditions. Heart rate was significantly greater for active THC and modafinil conditions compared to placebo. Systolic blood pressure was significantly lower for active THC and modafinil conditions compared to placebo. Diastolic blood pressure was a significantly greater for active modafinil conditions.

Fig. 2

Subjective responses to selected items on DEQ under 15 mg active THC plus 400 mg active modafinil (THC+MOD), 15 mg active THC plus placebo (THC+PLA), placebo plus 400 mg active modafinil (PLA+MOD), or placebo plus placebo (PLA+PLA) conditions. There were significantly greater ratings of “feel high,” “feel sedated,” and “feel the drug strength” for the two active THC conditions.

Fig. 3

Subjective responses to selected items on ARCI under 15 mg active THC plus 400 mg active modafinil (THC+MOD), 15 mg active THC plus placebo (THC+PLA), placebo plus 400 mg active modafinil (PLA+MOD), or placebo plus placebo (PLA+PLA) conditions. There were significantly greater ratings of sedation, dysphoria, and marijuana for active THC conditions. Compared to other conditions, the THC+MOD condition had significantly lower ratings of drug-induced euphoria. Compared to THC+PLA and PLA+MOD conditions, the THC+MOD condition has significantly lower ratings on the intellectual efficiency and energy subscale.

Fig. 4

Total recall on the HVLT (a) and target sensitivity and response bias on the RVIP (b) under 15 mg active THC plus 400 mg active modafinil (THC+MOD), 15 mg active THC plus placebo (THC+PLA), placebo plus 400 mg active modafinil (PLA+MOD), or placebo plus placebo (PLA+PLA) conditions.