Distinct Acute Effects of LSD, MDMA, and D-amphetamine in Healthy Subjects

 I have read social media articles about the different effects of Lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), and D-amphetamine to assist psychotherapy and to treat attention-deficit/hyperactivity disorder. This research investigates 5h3 acute autonomic, subjective, and endocrine effects of single doses of LSD (0.1 mg), MDMA (125 mg), and D-amphetamine (40 mg) in 28 healthy subjects (healthy refers to a person who does not have the disorder or disease being studied). This is an experimental research because more than one group is created, followed by a manipulation of a given experience for these groups, and a measurement of the influence of the manipulation. I think the study was well designed since it was double-blinded, used different doses of each drug, and used informative figures that were helpful to explain the results. 

Some previous clinical trials reveal that the quality of acute psychedelic experience in response to psilocybin or LSD predicts long-term changes in mental health and well-being in patients. The purpose of this study is to compare the “subjective and autonomic effects of all three substances over time and determine plasma concentration-time profiles (pharmacokinetics)” (Holze). The 60-item Adjective Mood Rating Scale (AMRS) was administered 1 hr before and 1.5hr, 4hr, and 11hr after drug administration. The study hypothesized that LSD would have different effects on consciousness compared with MDMA and D-amphetamine. Also, the study predicted that MDMA would produce greater increases in plasma concentrations of oxytocin than LSD and D-amphetamine.  

For methodology, this research was double-blind and placebo-controlled with four experimental test sessions to investigate the responses to LSD, MDMA, D-amphetamine, and placebo in female and male participants. Participants were provided  written consent before participating in the study and were paid for their participation. Five participants had previously used a hallucinogen, including LSD, DMT, and salvia divinorum, while eight participants had used MDMA . Some participants had never used any illicit drugs with the exception of cannabis. Urine drug tests were performed before each test session and no substances were detected. The study included four 12-hr experimental sessions, a screening visit, an end-of-study visit, and a psychiatric interview. For each  experimental session, only one research subject and one investigator were present. The rest of the participants were interacting with the investigator, resting, or listening to music via headphones. LSD, MDMA, and D-Amphetamine sulfate were administered in the form of gelatin capsules as a single oral dose. At the end of each session, the participants were asked to guess their treatment assignment. 

The first result showed that LSD produced a greater response than both MDMA and D-amphetamine reflected by the higher increases in ratings of “good drug effect” in the survey. According to their ratings, LSD induced a reduction in talkativeness and speed of thinking compared with MDMA and D-amphetamine (Table 1) (Figure 1). Furthermore, LSD produced greater “introversion,” “inactivity,” “emotional excitation,” and “anxiety” compared with MDMA and D-amphetamine. On the other hand, MDMA and D-amphetamine increase “extraversion” compared with LSD. D-Amphetamine also increased “activity” and “concentration” compared with LSD. The only drug that induced alterations of mind by large increases on all subscales of the 5D-ASC was LSD (Figure 3a). All three drugs increased blood pressure, heart rate, and body temperature compared with placebo. To sum up, only MDMA increased plasma concentrations of oxytocin. This study shows that LSD produces stronger and more distinct subjective effects compared with MDMA and D-amphetamine.



Holze, F., et al. “Distinct Acute Effects of LSD, MDMA, and D-amphetamine in Healthy Subjects” Nature News, Nature Publishing Group, 16 Nov, 2019.