LSD

Key Insights

• 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.
• 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.
• 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.

Author: Floris Wolswijk is the founder of Blossom. He started Blossom in 2019 to help translate psychedelic research to a broader audience. Since then, he has grown the database to encompass 2000 papers and hundreds of other valuable resources. Floris has an MSc in Psychology and offers psychedelic-assisted coaching at FLO.

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
• 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.

Europe

Researchers in Basel, the city in which Albert Hofmann discovered LSD, are now testing the effects of this psychedelic on the human fear response. Researchers have shown that 100 micrograms of LSD are sufficient to reduce the fear response in healthy subjects who are shown pictures of others in a fearful state. They observed reduced activity in the amygdala (emotional centre), which was mirrored by the subjects’ reports that those who received the LSD dose experienced less fear than those who did not.

How LSD specifically, and psychedelics in general, are metabolised in the body has a direct influence on the intensity of the ‘lived’ experience. Researchers found that people who lacked copies of the CYP (Cytochrome P450) gene, which codes for an enzyme that breaks down LSD, had up to 75% more exposure, as measured by their blood plasma levels, of LSD. These participants had more intense and longer-lasting trips. Information on genetic differences could lead to the development of more personalised medicines or to more personalised dosing.

Another study in Switzerland, one of the few double-blind, placebo-controlled studies with LSD in patients, was conducted with 11 people who were suffering from life-threatening diseases. The patients underwent two sessions with either 200 micrograms or 20 micrograms (active placebo) LSD. The study found a significant decrease in anxiety and a trend towards lower scores on a measure of depression.

In 2019, the Beckley Foundation, in collaboration with Maastricht University, concluded one of the first double-blind, placebo-controlled studies on microdosing LSD and its effects on pain management, mood and cognitive function. Currently, the foundation is researching the impact that a fixed microdose of LSD can have on amplifying brain plasticity. It is hoped that the results of these studies will lead to LSD becoming a possible treatment for a range of conditions such as mood disorders, age-related cognitive decline/mild impairment, chronic pain, brain rehabilitation and addiction.

A neuro-pharmaceutical company, MindMed, is also funding research into the effects of microdosing LSD and its impact on creativity and focus, with a view to developing a new treatment for the symptoms of ADHD. In April 2020, MindMed filed a patent in the US (preserving worldwide rights) for a neutraliser
technology intended to shorten or eliminate the effects of an LSD trip during a therapy session. If sufficiently developed, this technology could effectively act as an ‘off-switch’ to an LSD trip. This research is a collaboration between MindMed and the University of Basel’s Liechti Laboratories.

At Imperial College London (ICL), the Centre for Psychedelic Research (CPR) was set up last year, backed by five founding investors who contributed £3 million to get the project off the ground. The stated purpose of this research centre is two-fold: to investigate the potential of psychedelics in treating mental health disorders and secondly to probe the basis of human consciousness using the most modern imaging techniques available. One of the first studies conducted by the Psychedelic Research Group at ICL, prior to the establishment of the CPR, was a study on the effects of LSD on brain activity, using brain imaging techniques.

North America

Researchers at the Eleusis Benefit Corporation in New York are seeking to leverage the anti-inflammatory activity of low doses of LSD to stave off Alzheimer’s disease. The company so far has been successful in phase I clinical trials, which demonstrated the safety of doses up to 20 micrograms in geriatric populations. Next, the researchers will investigate whether the anti-inflammatory activity of LSD is neuroprotective against Alzheimer’s.

In June 2020, MindMed announced a phase IIb commercial drug trial, for the treatment of anxiety disorders, officially known as Project Lucy. The trial will focus on experiential doses of LSD, administered by a therapist. The company’s aim will be to submit an application for an investigational new drug (IND)
with the US FDA.

Oceania

In January 2020, the Ministry of Health approved the first LSD microdosing study in New Zealand. Researchers at the Centre for Brain Research at the University of Auckland had previously engaged in other multidisciplinary research projects using LSD, including the same brain imaging study conducted by researchers from ICL.

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.