Long before hippie poster boy Timothy Leary invited the world to "Turn on, tune in and drop out", a group of pioneering psychiatrists working in Canada began to treat alcoholics with lysergic acid diethylamide (LSD), and reported unprecedented recovery rates.

Far from being at the fringes of medical research, their work was fully supported and funded by the Canadian government, and became a promising new area of research that played a role in modernising the field of psychiatry. But despite the encouraging results, studies of LSD therapy ended abruptly in the late 1960s, and did not resume again until some 40 years later.

At the cutting edge of early psychedelic research was one Humphry Osmond (1917-2004), a British psychiatrist at the Weyburn Mental Hospital in the Canadian province of Saskatchewan. It was Osmond who gave the novelist Aldous Huxley his first dose of mescaline in 1953, and coined the term "psychedelic" in 1957.

Between the years of 1954 and 1960, Osmond and his colleague Abram Hoffer treated some 2,000 chronic alcoholics with LSD. None of these patients had responded to other treatments, and yet, Osmond and Hoffer reported that up to 45% of those treated with a single large dose of the drug abstained from drinking for at least a year afterwards.

Other researchers in Canada, Britain, the United States and elsewhere began experimenting with LSD therapy, and by the time the drug hit the streets in the early 1960s, there were more than a thousand published research papers that described promising results in over 40,000 patients.

These studies took place alongside trials of newly developed compounds such as the antipsychotic chlorpromazine and the tricyclic antidepressant imipramine. This body of work effectively established the new field of psychopharmacology, which led psychiatrists to abandon the psychoanalytical approach they had been using since the turn of the century, and begin to consider alcoholism and mental illnesses in terms of disrupted brain chemistry.

Although the results of many of the early studies into LSD therapy were promising, investigations of the potential therapeutic benefits of the psychedelic drugs stopped towards the end of the decade, for two main reasons.

First, some began to question the methods used in the studies, arguing that they lacked scientific rigour, and few, if any, other researchers managed to replicate the high recovery rates reported by Osmond and Hoffer. Many therefore viewed the early studies as providing nothing more than anecdotal evidence for the therapeutic benefits of LSD.

Second, and more importantly, the cultural and political climate became less conducive to psychedelic research. LSD became a popular recreational drug towards the end of the 1960s, and came to be associated with the hippie counterculture, anti-authoritarianism and social disobedience. As a result, research funding quickly dried up, and the drug was eventually criminalised by the US and other governments in 1970.

The past decade has seen renewed interest in the potential therapeutic benefits of LSD and other psychedelic drugs, and the availability of sophisticated techniques such as functional neuroimaging is beginning to provide fresh insights into how they affect the brain.

The new research confirms that the psychedelic drugs do indeed have therapeutic value for a number of psychiatric conditions, including depression, obsessive-compulsive disorder (OCD) and schizophrenia. It also points to various brain mechanisms which may underly their beneficial effects.

We now know that the so-called classical hallucinogens (LSD, psilocybin and mescaline) activate 5-HT2A receptors – which normally bind the neurotransmitter serotonin – in the deep layers of the prefrontal cortex. This in turn alters nerve cell signalling mediated by the transmitters glutamate and dopamine, and may also lead to changes in the strength of connections between neurons in the cortex and other parts of the brain.

Serotonin and dopamine convey messages in the brain circuits involved in mood, and psychedelic drugs apparently alleviate the clinical symptoms of mood disorders by modulating the activity of the cells in these circuits and by modifying their connections.

The very latest research shows that ketamine, an anaesthetic with hallucinogenic properties, can reduce the symptoms of depression quickly and effectively, and that MDMA (popularly known as ecstasy) can be beneficial to sufferers of post-traumatic stress disorder when used in combination with behavioural therapy.

By contrast, new research into the effects of the classical hallucinogens has progressed at a much slower pace, probably because these drugs are categorised as Class A in the UK (Schedule I in the US), and researchers who wish to obtain them therefore face numerous regulatory barriers.

Nevertheless, it now seems quite clear that psychedelic drugs have enormous potential for treating a wide variety of psychiatric conditions. Much still remains to be discovered about exactly how they affect the brain, however.

For example, optimising their clinical benefits will require a better understanding of how their molecular structures are related to their activity, and of how each drug can be combined with psychotherapeutic approaches to achieve the best results.

Furthermore, because most psychedelics can mimic the symptoms of naturally occurring psychoses – they can, for example, induce hallucinations and disorganised thought processes – future research may reveal some of the brain mechanisms underlying schizophrenia and related conditions.

The debate that occurred in the 1960s about the therapeutic use of LSD mirrors the one taking place today over the use of MDMA, so the history of LSD experimentation could provide valuable lessons about how to incorporate these controversial drugs into modern medicine.

Moheb Costandi is a molecular and developmental neurobiologist who writes the Neurophilosophy blog

Further reading

The secret history of psychedelic research (Neurophilosophy)

Serotonin, psychedelics and depression (The Neuroskeptic)

Ketamine for depression: yay or neigh? (The Neurocritic)

Visions of a psychedelic future (Mind Hacks)

Vollenweider, F. X. & Kometer, M. (2010). The neurobiology of psychedelic drugs: implications for the treatment of mood disorders. Nature Reviews Neuroscience; 11: 642-651.

• Moheb Costandi writes the Neurophilosophy blog