An exploratory study of the combined effects of orally administered methylphenidate and delta-9-tetrahydrocannabinol (THC) on cardiovascular function, subjective effects, and performance in healthy adults

Abstract

Methylphenidate (MPH) is commonly prescribed for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), and is often used illicitly by young adults. Illicit users often coadminister MPH with marijuana. Little is known about physiologic and subjective effects of these substances used in combination. In this double-blind, cross-over experiment, sixteen healthy adult subjects free from psychiatric illness (including ADHD) and reporting modest levels of marijuana use participated in 6 experimental sessions wherein all combinations of placebo or 10 mg oral doses of delta-9-tetrahydocannibinol (THC); and 0 mg, 10 mg and 40 mg of MPH were administered. Sessions were separated by at least 48 hours. Vital signs, subjective effects, and performance measure were collected. THC and MPH showed additive effects on heart rate and rate pressure product (e.g., peak heart rate for 10 mg THC + 0 mg, 10 mg, and 40 mg MPH = 89.1, 95.9, 102.0 beats/min, respectively). Main effects of THC and MPH were also observed on a range of subjective measures of drug effects, and significant THC dose × MPH dose interactions were found on measures of “Feel Drug,” “Good Effects,” and “Take Drug Again.” THC increased commission errors on a continuous performance test (CPT) and MPH reduced reaction time variability on this measure. Effects of THC, MPH, and their combination were variable on a measure of working memory (n-back task), though in general, MPH decreased reaction times and THC mitigated these effects. These results suggest that the combination of low to moderate doses of MPH and THC produces unique effects on cardiovascular function, subjective effects and performance measures.

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.…”

“…Further evidence has accumulated in support of acute exposure to cannabinoids impairing focused, divided, or sustained attention, often in a dosedependent manner (36,37,42,43,68,70,71,(86)(87)(88). In cases where lesser impairments were observed, this may be due to the development of tolerance among daily users (76,89,90).…”

Substance Use Among Adolescents with Attention-Deficit/Hyperactivity Disorder: Reasons for Use, Knowledge of Risks, and Provider Messaging/Education

“…The combination of marijuana and stimulant medication is associated with increases in peak heart rate and subjective effects, and slower reaction times, compared to use of either substance alone. 11 Alcohol may enhance the adverse/toxic effects of stimulants, 12 increase risk of central nervous system depression in combination with alpha 2 agonists, and could result in temporary liver impairment which would contraindicate the use of atomoxetine. 13 Given these risks, adolescents with ADHD should be informed about the possible dangerous outcomes of using ADHD medications in combination with alcohol, marijuana, and/or illicit drugs.…”

Medical Cannabis for Pediatric Moderate to Severe Complex Motor Disorders

“…Mood deterioration has not been previously reported in patients treated with a combination of THC and methylphenidate. 28 Limitations of our study include the small sample size, which makes rejection of the null hypotheses difficult. Additionally, titration of the medication was slow, so that the total time on the optimal dose was limited.…”