The Colourful Past and Shimmering Future of Lysergic Acid Diethylamide in Psychiatry
Lysergic acid diethylamide is a psychedelic, which many feel has huge therapeutic potential, and despite the fact that it came into being as a medical substance, politics have grabbed it from the medical speciality and thrust it into the legal system. LSD was classed as an A substance in the UK and a Schedule 1 substance in the USA in 1966, meaning, by definition, that it has ‘no currently accepted medical use and a high potential for abuse,’ which is odd considering there is a fairly rich literature describing its potential for patients, and no reported deaths caused by the physical effects of LSD.
Due to the intense and rather long-lasting experience, most people who have tried the drug do not use it more than a handful of times and it is not addictive.
Pharmacokinetics and Pharmacodynamics
LSD has a plasma half-life of around 5 hours. The experience can last up to 12 hours, and ‘afterglow’ effects can be felt for several days.
LSD is a nonselective 5-HT agonist, with the main psychedelic effects resulting from its action at 5-HT2A receptors. It is thought that the hallucinogenic effects come about through increased glutamate release and associated excitation in certain parts of the brain.
Having stated that LSD is physiologically safe, it can be psychologically harmful for people with pre-existing mental illness, especially those with a personal or family history of schizophrenia as it could trigger an episode of psychosis. However, compared to other drugs such as amphetamine, cocaine, and cannabis, it appears to occur less frequently. The results of one poorly controlled animal study in the 60’s looking at doses far in excess of a clinical or street dose, prompted a rumour to spread that LSD damages chromosomes. Thankfully this is not the case.
Swiss chemist Albert Hofmann was investigating lysergic acid for its ability to induce vasoconstriction. He synthesised many derivatives of the ergot fungus found on rye, and in 1938 he produced a substance he named lysergic saure diethylamide-25 (LSD), (saure being the German word for acid). Having shelved it though, LSD’s psychoactive properties were not realised until five years later when Hofmann decided to synthesise a fresh batch, resulting in a little of the product being absorbed through his fingers. What resulted was a 2 hour episode of dizziness and hallucinations; intense colourful shapes filled his mind.
Hofmann, under the supervision of his colleagues 3 days later, on April 19th 1943, decided to take 250 micrograms of LSD. He believed this amount to be the threshold dose, but was actually 12 times greater. Within an hour, Hofmann was having an even more intense psychedelic experience than the previous one, and wished to go home. Due to the wartime restrictions on vehicles, the journey had to be made by bicycle. When his neighbour came to check on him, Hofmann thought she was “a malevolent witch,” and lay on his bed, thinking he was dying. Convinced the LSD had poisoned him, a doctor was called, who checked him over, assuring him that the only physical sign he could find were a pair of incredibly dilated pupils.
The experience slowly became a positive one, and Hofmann relaxed, enjoying the ‘kaleidoscopic, fantastic images,’ dancing before him.
Sandoz laboratories then spent a few years putting LSD through phase one investigations, testing its toxicity and safety. They concluded that despite the powerful mental effects, it appeared to be virtually physiologically inert, with mild fluctuations of pulse and blood pressure. Subsequently, LSD was found to be safe for human consumption, and was distributed to psychiatrists across the globe under the brand name Delysid.
In 1954, Dr Ronald Sandison, a psychiatrist in Gloucestershire, used LSD to trigger a therapeutic response from 36 treatment-resistant patients. Sandison and his colleagues built an LSD clinic attached to the local hospital, and there they saw up to 5 patients a week. Sandison developed a program of psycholytic (literally meaning ‘mind-loosening’) therapy for treatment of illnesses such as schizophrenia and severe depression. Low doses (20 micrograms) of LSD were used repeatedly with small dose increases until progress was made, alongside psychotherapy. All patients seen at the LSD clinic had already been in traditional psychotherapy where they had failed to progress as hoped. Patients could retire to their rooms alone where there were art materials and music, or talk to nurses or medical registrars.
In the late 1950’s, psychiatrist Dr Humphry Osmond (who coined the term ‘psychedelic,’ meaning ‘mind-manifesting’) gave LSD to people with alcoholism who had failed to quit drinking. Based on the understanding that many people could only stop after an episode of delirium tremens, it was thought that receiving a high dose of LSD would offer a similar state to this condition of withdrawal. Thus psychedelic therapy involved one high dose given to a patient alongside psychotherapy. Osmond believed that it enabled patients to view their condition from a new perspective. No SSRI (antidepressant) can do such a thing. He claimed that after one year, 50% of participants had not had an alcoholic drink, a hugely successful statistic that has never been reproduced by any other method.
In 1956, Bill Wilson received a dose of LSD. The experience allowed him to revisit a spiritual experience that captured him a few years before and enabled him to overcome his addiction to alcohol. He felt that the experience broke down barriers built by the ego that stood in the way of the cosmos and God, and believed that LSD could make a big difference to the lives of many still suffering. Research shows that the more intense a spiritual experience, the more likely a person is to remain abstinent. Wilson founded Alcoholics Anonymous, and tried to bring LSD into the program (the Twelve Steps), but it caused huge controversy amongst members and was soon forgotten.
The Law Takes Over
In the 60s, LSD was being used recreationally by more and more members of the public. Scare stories about people losing their minds started circulating in the press, and in 1966 it was banned worldwide. This did little to stop illicit use, but halted medical research instantly.
In 2009, government advisor Professor David Nutt proposed that LSD be moved from Class A to Class B, claiming it was less harmful than alcohol and tobacco. Despite producing a comprehensive evidence-based report supporting this, he was sacked. The current prohibition laws are not based on scientific grounds; there is no correlation between the Misuse of Drugs Act and harm to the person taking the drug, society, or risk of dependence.
Despite these barriers, there has been a recent movement towards studying psychedelics to assist psychiatric patients, as well as investigations into how the brain works normally, and consciousness.
There is a stigma surrounding psychedelic research on par with that of mental illness. It is often seen as career suicide to work with psychedelics, and there is little funding, except from groups such as the Multidisciplinary Association for Psychedelic Studies (www.maps.org), and The Beckley Foundation (www.beckleyfoundation.org). For some researchers, the potential for finding a cure for serious illnesses such as PTSD, depression, OCD and addiction is enough to struggle on, providing legitimate research into psychedelics.
Dr Robin Carhart-Harris, a research associate in neuropsychopharmacology at Imperial College, recently completed a neuroimaging study (fMRI and MEG) of the brain on LSD. Patients in the study who had taken LSD made fewer verbal references to themselves in the past and future compared to placebo; ‘living in the moment,’ which many philosophical and religious teachings suggest is the route to happiness. This study therefore supports LSD’s potential role in depressive disorders and anxiety.
Psychiatry sees many patients that are resistant to current available forms of treatment. For the sake of our patients, we must look at all possible ways that we can help treat or even cure them. psychedelic drugs, including LSD, may be one such way.