For nearly forty years, medical research on prohibited drugs like LSD, MDMA, or psilocybin was considered taboo. But recently, the scientific community is showing increased interest in studying the therapeutic potential of these once-demonized drugs.
Most of these research studies focus on one specific drug at a time, but a team of Swiss researchers recently conducted the first controlled study to compare three different drugs head-to-head-to-head. The study, recently published in the Neuropsychopharmacology journal, directly compares the effects of LSD, MDMA, and dextroamphetamine (D-amphetamine) — an Adderall-like drug prescribed for ADHD.
Each of these drugs are used recreationally. The hallucinogenic effects of LSD became popular during the counterculture movement of the ‘60s, and the use of MDMA — better known as ecstasy or Molly — rose to fame in clubs during the ‘80s. D-amphetamine, basically an off-brand of Adderall (both of which are a close relative to meth), is fully legal and prescribed for attention disorders, but often abused for its stimulant effects.
LSD and MDMA are both currently classified as Schedule I drugs with no medical value, but researchers have recently discovered that both of these compounds show major potential for therapeutic use. D-amphetamine is legally used to treat attention-deficit/hyperactivity disorder (ADHD), although newer amphetamine-based drugs, like Adderall or Vyvanse, tend to be more popular prescriptions these days.
“MDMA and LSD are both newly used in psychiatric research to treat PTSD and anxiety disorder respectively,” said study co-author Matthias Liechti, professor of clinical pharmacology at the University Hospital Basel in Switzerland, to PsyPost. “However, differences in the acute effects of these two acutely psychoactive compounds have never been compared directly.”
In the new double-blind study, 28 healthy subjects were given a single 0.1mg dose of LSD, a 125mg dose of MDMA, a 40mg dose of D-amphetamine, or a placebo in randomized order. Each individual drug session was administered at least ten days apart to allow subjects to recover. Researchers recorded subjects' subjective experiences with each drug, while also measuring the autonomic and endocrine effects of each chemical.
Out of the three drugs, LSD had the most pronounced subjective effects. Subjects reported higher ratings of “any drug effect,” “good drug effect,” “bad drug effect,” “ego dissolution,” and “emotional excitation,” compared to the other two drugs. Subjects also reported higher levels of introversion, inactivity, and anxiety when using LSD, compared with MDMA or D-amphetamine. LSD was also the only drug of the three that “induced marked alterations of mind,” the study reports.
Subjects taking any of the three drugs reported increased ratings of feeling “talkative” or “open.” MDMA and D-amphetamine both produced higher ratings of “concentration” and “extraversion” compared with LSD. MDMA was linked to higher ratings of “any drug effect,” “good drug effect,” “drug liking,” and “drug high” compared with D-amphetamine. All three drugs increased pupil size, blood pressure, heart rate, and body temperature compared with the placebo.
“LSD has much more pronounced and overwhelming subjective effects than MDMA, even when MDMA is used at a relatively high dose and LSD at a moderate dose,” said Liechti to PsyPost. “There is a significantly greater experience of ‘ego dissolution’ with LSD compared with MDMA. There is also a greater risk of anxiety with LSD. However, there may also be greater positive effects such as feelings of bliss.”
Only three of the participants had ever used LSD, but 96 percent of all subjects were able to correctly identify when they had been dosed with this powerful hallucinogen. Eight of the participants had used MDMA before, and 75 percent of subjects were able to correctly identify whether they had been dosed with MDMA or D-amphetamine.
The authors note the limitations of their research, but hope that their study will be a springboard for further research. “Only single dose levels were compared,” Liechti explained. “A comprehensive comparison would need more than one dose. Additionally, the study was done in healthy subjects. The relevance for patients needs further study.”
“A similar comparison between different psychedelics such as LSD, psilocybin, and mescaline is warranted,” Liechti recommended. “Both LSD and psilocybin have a potential to become medications and it will be of interest what the differences in benefits and risks are.”