A Preliminary Investigation of Individual Differences in Subjective Responses to D-Amphetamine, Alcohol, and Delta-9-Tetrahydrocannabinol Using a Within-Subjects Randomized Trial

Abstract

Polydrug use is common, and might occur because certain individuals experience positive effects from several different drugs during early stages of use. This study examined individual differences in subjective responses to single oral doses of d-amphetamine, alcohol, and delta-9-tetrahydrocannabinol (THC) in healthy social drinkers. Each of these drugs produces feelings of well-being in at least some individuals, and we hypothesized that subjective responses to these drugs would be positively correlated. We also examined participants' drug responses in relation to personality traits associated with drug use. In this initial, exploratory study, 24 healthy, light drug users (12 male, 12 female), aged 21-31 years, participated in a fully within-subject, randomized, counterbalanced design with six 5.5-hour sessions in which they received d-amphetamine (20mg), alcohol (0.8 g/kg), or THC (7.5 mg), each paired with a placebo session. Participants rated the drugs' effects on both global measures (e.g. feeling a drug effect at all) and drug-specific measures. In general, participants' responses to the three drugs were unrelated. Unexpectedly, "wanting more" alcohol was inversely correlated with "wanting more" THC. Additionally, in women, but not in men, "disliking" alcohol was negatively correlated with "disliking" THC. Positive alcohol and amphetamine responses were related, but only in individuals who experienced a stimulant effect of alcohol. Finally, high trait constraint (or lack of impulsivity) was associated with lower reports of liking alcohol. No personality traits predicted responses across multiple drug types. Generally, these findings do not support the idea that certain individuals experience greater positive effects across multiple drug classes, but instead provide some evidence for a "drug of choice" model, in which individuals respond positively to certain classes of drugs that share similar subjective effects, and dislike other types of drugs.

Trial registration: ClinicalTrials.gov NCT02485158.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. CONSORT Diagram.

Number of participants screened, randomized and completing the study, with reasons for exclusion and discontinuation.

Fig 2. Changes from pre-capsule/drink ratings in DEQ scales.

Mean changes for “Feel Drug” (top row), “Like Drug” (middle row), and “Dislike Drug” (bottom row) following AMP (left column), ALC (middle column) and THC (right column) relative to their corresponding placebos across the session. Vertical dashed lines indicate time of capsule or drink administration. The values represent the mean ± s.e.m for each timepoint. %P<0.05, #P<0.01, *P<0.001.

Fig 3. Mean peak changes from pre-capsule/drink in DEQ and ARCI scales.

Left: Mean peak change from pre-capsule in DEQ “Feel,” “Like,” “Dislike,” “High,” and “Want More” scores by drug. Right: Mean peak change in ARCI A, MBG, LSD, BG, PCAG, and M scores by drug. The values represent the mean ± s.e.m at timepoint 3. %P<0.05, #P<0.01, *P<0.001, &P = .051.

Fig 4. Scatter-plot of peak effects of ALC and THC on the DEQ "Want More" scale.

Subjects who wanted more ALC reported wanting less THC (r = -.47, p = 0.02).