A trip through time: the past, present and future of psychedelics

LSD and psilocybin: brain-ravaging psychedelics or the future of mood disorder treatment? After an almost 40 year ban on medical research using psychedelics, pressure is mounting to make studies using these potentially revolutionising psychiatric drugs less of a political battle. Not only have these substances been unfairly accused of causing long-term psychiatric problems, but hallucinogenic substances have been cited as candidates for the evolution of religion, have evolved new genres of music, art and literature, and have inspired geneticists and technologists alike. So why, considering that botulinum toxin (the most toxic substance known to humankind – less than 2kg could kill everyone on Earth) is used freely in medical research, are these mysterious substances so shunned by society? Let’s consider what is known and unknown about these controversial substances, and explore their use from ancient tribal rituals to modern medicine.

Hallucinogens as the birth of spirituality

For thousands of years, religious gatherings of indigenous tribes throughout the world have been centred around psychoactive plant use. For example Teonanacatl, a type of psilocybin (magic) mushroom, literally meaning ‘divine flesh’, was thought to have been ingested during Aztec religious ceremonies and inspired spiritual experiences which somehow connected the Aztec people to their god. Similarly fascinating tales come from the ‘soma’ of India, ‘peyote’ of Native Americans, and ‘hoasca’ of the Amazon tribes. Some believe that such substances may have given rise to the modern idea of religion. It’s a controversial theory; however what can’t be denied is that they have certainly inspired creators of literature, art, technology, music, medicine – the list goes on. Aldous Huxley, Steve Jobs and Francis Crick were all self professed users.

The idea behind these religious epiphanies is that LSD encourages introspection: it is thought to provide an outward reflection of the user’s internal life and to encourage self-improvement.  In fact, a Brazilian religious movement founded in the 1930s continues to use a psychoactive concoction which is drunk before religious worship begins, followed by hours of singing and self-reflection.

Despite their debatably profound influence on human cultural evolution, it was not until the 1950s that the various chemical identities and thus mechanisms of action were elucidated.

Hallucinogens as the sustenance of sociability

In 1940s Basel, Switzerland, the chemist Albert Hofmann was searching for an analeptic (pharmacological respiratory aid) for the pharmaceutical company Sandoz. Upon waking from an unexpected intoxicated, kaleidoscopic dream, Albert realized that his fingers had managed to synthesise and absorb some of a new and mysterious chemical: lysergic acid diethylamide. Keen to experiment with an increased dose, he intentionally ingested more, giving birth not only to a potent drug with huge potential, but also a day dedicated to the international celebration of (among other things) bicycles.

Sandoz quickly recognized the potential of LSD to revolutionize psychiatric treatment and sold it under the trade name Delysid during the 1950s and 60s. Its clinical benefits of relieving symptoms of anxiety, alcoholism and severe pain were used to treat 2000 chronic alcoholics who had not responded to any other treatment. Within the group that the two psychiatrists Osmond (himself a user and advocate of its use) and Hoffer treated, a remarkable 45% withdrew from alcohol for a year after a single dose of Delysid. Unfortunately this apparent wonder drug was not going to lie beneath the radar for long.

Hallucinogens as the destruction of morality

Things began to turn sour with the birth of Project MKUltra in the 1950s. In response to the Russian government using the Danyz that Sandoz had released to the global marketplace as an alleged ‘truth serum’, the USA began to investigate its potential use. The main goal of the CIA was to assess whether LSD could be used to alter the loyalty of Russian spies and subsequently squeeze secrets out of them. To test this theory, LSD was administered to members of the public without their knowledge or consent, who were then followed and observed. After secret surveillance of a huge number of individuals, some of whom experienced ‘bad trips’ and have consequently gone on to suffer PTSD, the effects of LSD were found to be too unpredictable and its potential use as a weapon of war was discarded.

The evangelism of LSD by the 1960s counterculture saw a surge in black market LSD trading; however authorities responded with claims that due to its alleged lack of therapeutic benefits (despite it having many), and potential for abuse (can’t everything be abused?), it would subsequently be banned.

Hallucinogens as the expansion of consciousness

The hallucinogens mimic serotonin (also called 5-HT), an endogenous neurotransmitter with a vast array of roles. Serotonin mediates changes in the brain by acting on one of its 15 receptor subtypes which are scattered throughout the central nervous system. As far as we know, hallucinogens act specifically on the 5-HT(2A) receptor which leads to release of the excitatory neurotransmitter glutamate from presynaptic thalamic afferents, going on to affect mainly the prefrontal cortex and the anterior cingulate cortex which are areas thought to be involved in emotion, introspection and cognitive processing.

Until a few years ago, the prevailing view was that hallucinogens broadened perception by enhancing brain connectivity. However, more recent evidence points to enhanced inhibition of the brain during a trip. For example in a recent study carried out by Carhart-Harris and colleagues, psilocybin was administered to 30 patients while changes in brain activity were monitored with fMRI. During the psilocybin trip the researchers noticed that activity in the aforementioned areas appeared to be reduced, leading to the suprising conclusion that psilocybin actually inhibits the brain regions that might constrain consciousness in the normal waking state.

Of course these drugs do not come without some downsides, otherwise there really would be no reason to keep them illegal. Anxious or poor mental states can induce ‘bad trips’, and it is also claimed (and disputed) that LSD use can lead to depression, psychosis and PTSD, although it’s generally thought that this occurs in people who are already predisposed to such conditions. There are also problems with the understanding of the drugs’ pharmacology: the mechanisms behind the addiction potential of LSD are not as clear cut as previously thought. Studies using higher concentrations of LSD show that this may activate postsynaptic dopaminergic neurons which are thought to have a strong role in addiction.

Hallucinogens as the future of psychiatry

Halting of psychedelic research almost half a century ago means it’s hard to tell for certain how much potential lies within this class of drugs, but there is evidence which suggests that psychedelics are useful in the treatment of stress and anxiety in cancer patients, OCD, neuropathic pain and cluster headaches. Given that current treatment options for mood disorders are limited and success is hugely variable between individuals, and that the effects of psychedelics on the brain are thought to model an early stage of psychosis, the idea of regulated psychedelic use in medical research shedding light on the nature of these conditions seems undeniably attractive. Admittedly in the last decade, steps have been made in the right direction. However, licences are still hard to obtain and funding is scarce.  To bring psychedelics back into medical research, governments must be convinced of these therapeutic benefits.  That’s pretty difficult considering that they’re already banned, so it is incredibly difficult to conduct the appropriate research. Unless the government’s real fear is the unlikely event of tripping mice exercising world domination, they could do worse than to resolve this catch-22.