LSD is undoubtedly the most significant drug acting on the brain ever discovered. In the decades that followed its discovery, it was hailed as a powerful scientific tool for investigating consciousness and the causation and treatment of mental illness. It was widely studied in the treatment of addiction and mood disorders with positive outcomes, and helped develop new insights into the nature of psychosis.
Exactly how LSD produces its characteristic mind-altering effects is unknown, and research has been heavily restricted since LSD was banned in 1966. However, our work with Prof David Nutt and Dr Robin Carhart-Harris in the Beckley / Imperial Research Programme has overturned the fifty year ban, and is beginning to shed light on these mechanisms for the first time.
Using the most advanced brain imaging techniques (arterial spin labelling, functional MRI, and MEG) to measure brain blood flow, functional connectivity, and ‘brain waves,’ the Programme examines changes in the brain brought on by LSD, adding to the evidence base supporting its therapeutic potential while teaching us about consciousness itself. Our imaging data indicate that psychedelics (both LSD and psilocybin) produce a disorganised, or ‘entropic,’ brain state and a more disordered and fluid state of consciousness. This has important therapeutic implications, as certain mental health conditions can be conceptualised as ‘inflexible’ and ‘excessively organised’ patterns of thought, and psychedelics may break down these patterns by dismantling the brain activity patterns upon which they rest. We are also exploring the interaction between LSD and the emotional response to music, which may further enhance its therapeutic potential.
In addition to investigating the effects of LSD on the brain, we are also working to examine its potential clinical benefits. In 2010, we collaborated with Dr Torsten Passie on a pilot study that demonstrated how 2-bromo-LSD, a non-psychoactive analogue of LSD, stopped or reduced the frequency of cluster headaches, a disease characterised by debilitating pain with almost no treatment options.
In collaboration with Dr Peter Gasser, we demonstrated the effectiveness of LSD for alleviating anxiety associated with terminal illness. This MAPS-led trial was the first LSD study to be approved by the U.S. Food and Drug Administration in 40 years. The results demonstrated that LSD paired with psychotherapy can alleviate ‘existential stress’ associated with terminal illness, putting the drug’s medical potential back in the spotlight for the first time since the 1960s.
We are also planning a clinical trial in collaboration with Michael Bogenschutz, building on his recent finding that psilocybin decreased alcohol drinking and craving and increased self-efficacy. To follow up this research, we are now preparing a ground-breaking double blind, placebo-controlled study of LSD-assisted treatment for alcoholism.
LSD was first synthesized by Albert Hofmann in 1938, but it was 5 years later, in 1943, when he discovered its psychoactive properties. Hofmann recognised the vast therapeutic potential of this drug and urged Sandoz, the pharmaceutical company where he worked, to start sending out samples to scientists and medical doctors worldwide. LSD was extensively researched and investigated throughout the 1950s and 60s, in particular as an adjunct to psychotherapy. Many of the studies demonstrated that it could be effective for treating mental disorders, and it was even examined by the U.S. Central Intelligence Agency (CIA), who thought the drug might be applicable to mind control and chemical warfare.
LSD became popular outside of research circles as well, and it was its recreational use, along with its importance in the counterculture movement, that led to a political firestorm. Fuelled by a number of scare stories in the media, governments came under pressure to criminalize possession, resulting in its prohibition. It is now controlled internationally by the 1971 UN Convention on Psychotropic Drugs, which means it is illegal except for scientific use. However, due to increasingly difficult regulatory hurdles and political pressure, most of the research of the effects of LSD on humans stopped.
The main psychoactive effects of LSD result from its effects on the serotonin system. Serotonin (abbreviated 5-HT for 5-hydroxytryptamine) is a naturally occurring brain chemical (‘neurotransmitter’) that binds to serotonin receptors. Numerous serotonin receptor subtypes have been discovered and are identified by number-letter combinations. LSD primarily binds to serotonin 2A (5-HT2A) receptors. However, it causes a different series of events to happen than serotonin does, which is why LSD has psychedelic effects and serotonin does not.
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