1. LSD was widely studied in the 1960s and generated over 1000 scientific papers. These studies showed positive developments in reducing anxiety during ‘end-of-life’ care, depression and alcoholism.
  2. Modern-day studies using fMRI are enlightening researchers about the way everyday consciousness functions and how the hierarchy of the brain is ‘flattened’ or ‘segregated’ under the influence of LSD.
  3. The duration of an LSD trip makes it a less likely candidate to be developed as a medicine. Its microscopic effective dose and widespread use in recreational microdosing do still show opportunities for the further study of this psychedelic.

Lysergic acid diethylamide (LSD, LSD-25, acid) is a serotonergic psychedelic. LSD binds to serotonin receptors, specifically the 5-HT2a receptor, as well as dopamine receptors (which psilocybin doesn’t bind to). The effects of LSD are noticeable at dosages measured in the millionths of a gram. Research studies use between 50 and 200 micrograms, which can produce effects for upwards of 12 hours. The study of LSD played a pivotal role in the discovery of the function of serotonin in the brain. Although widely studied in the 1960s, LSD is trailing behind psilocybin in terms of scientific interest.

Clinical trials and research

LSD was the most studied psychedelic around 60 years ago. Trials were conducted to study the effect of LSD on mood, alcohol dependence and, unfortunately also on patient populations with schizophrenia or autism, who hadn’t given consent to being administered a psychedelic. These questionable practices, in a time before ethics review boards, and the lack of any control groups who were given a placebo, means that much of the research was not up to today’s standards. The promising results from that time were also swept under the carpet when the counterculture adopted LSD as a recreational drug. The freeze on research has held back our understanding of mental health disorders for decades.

In the current era of research, 19 clinical trials have been conducted with LSD. Of those, four are phase II studies. The trials with LSD not only focus on mental health disorders but also serve a purpose for better understanding how our brains work. For instance, one study investigated the role of dopamine and serotonin after LSD administration and how this affected emotional processing. Studies like this can then inform those which more directly study mental health disorders in which emotional processing is disturbed.

The following is a list of conditions for which LSD has potential therapeutic benefits based on clinical trials and academic studies conducted to date:

  • Depression (MDD);
  • Anxiety and depression in patients with life-threatening disease;
  • Substance misuse, including alcohol, opioid and nicotine dependence;
  • Alzheimer’s disease (low-dose LSD);
  • Cluster headaches/migraines; and
  • Symptoms of OCD.

In the 19 clinical trials, 530 patients have been enrolled as of July 2021. Among the active trials are those investigating LSD for the treatment of anxiety, LSD for the treatment of depression, and LSD as a treatment for cluster headaches.

Legality of LSD worldwide 

The UN Convention on Psychotropic Substances (the ‘Vienna’ convention), 1971 identifies LSD as a Schedule I substance, a category of illicit drugs deemed to offer no medical benefit and with a high potential for abuse. The possession of LSD was made illegal in the US in 1968, but research continued until the late 1980s. Stringent government rules that prevented easy access for research purposes, in combination with less stellar results than hoped, ended any further research after that time.

The push for decriminalisation, as mentioned in our section on psilocybin, partly applies to LSD. The possession of small amounts of LSD (40 units or less) is decriminalised in Oregon as of February 2021. Some countries, including Mexico and Portugal, have decriminalised the possession of (small quantities) of drugs, including LSD.

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