#182 - David Nutt: Psychedelics & Recreational Drugs

David Nutt's interest began in early childhood, realizing that thinking came from the brain. He pursued brain science, moving from physiology to neurology, and finally to psychiatry, which he found 'wonderful' for observing every aspect of the brain.

Historically, every British drug law until 2016 was made at the behest of the US, with America largely defining and politically driving global drug policy since the 1930s.

Alcohol is consistently ranked as the most harmful drug overall due to its significant social impact and widespread use. For harm to the user, opiates, crack cocaine, and crystal meth are the most harmful.

One theory suggests alcohol's legality stems from its powerful pro-social effects and long history of cultural celebration, unlike cannabis which is not traditionally seen as a social drug. Another perspective points to historical disinformation campaigns against cannabis driven by the alcohol industry and drug enforcement agencies.

The crisis resulted from a perfect storm of excessive prescription of strong opioid painkillers, their diversion into society, and then a sudden stop in prescribing which drove dependent individuals to the black market. This led to the rise of potent and cheap fentanyls. Solutions include widespread drug testing to identify fentanyls and safer treatments for chronic pain like medical cannabis.

Ibogaine is thought to disrupt the over-learned, persistent patterns of over-attention and enhanced desire for drugs by 'shaking up' the brain, potentially breaking down habit circuits and allowing individuals to escape addiction.

Cocaine works by releasing dopamine and noradrenaline in the brain, providing energy, drive, focus, and purpose, followed by a severe crash. Risks include cardiac effects, paranoia, withdrawal symptoms, and the formation of cocaethylene when mixed with alcohol, which is more cardiotoxic.

Methamphetamine is similar to cocaine but longer-acting, pushing the dopamine system to depletion, which can lock users into a state where they can't function normally without the drug. There is less good evidence of cortical damage with modern use, but it definitely distorts dopamine pathways, affecting motivation and executive function.

Psychedelics were banned for political and social reasons, not due to inherent harms. The rise of the anti-Vietnam War hippie movement, fueled by LSD, was seen as a threat to the American way of life, leading to their vilification and subsequent ban despite extensive positive research.

Before its ban, 40,000 patients were studied, and 1,000 papers published on LSD, showing it was very safe, reduced suicide rates, and was effective in various therapeutic contexts, including alcoholism, without causing psychosis.

Ketamine is a dissociative anesthetic used off-label for depression, with effects lasting a few days. Esketamine is a patented enantiomer of ketamine, formulated for nasal inhalation (Spravato), licensed for treatment-resistant depression, and used a couple of times a week with less risk of tachyphylaxis.

Heavy recreational use of ketamine (e.g., grams daily) can lead to serious problems, including severe chronic cystitis that may cause bladder atrophy requiring resection, and a state of severe cognitive impairment that can mimic schizophrenia.

In a comparative study, psilocybin was found to be non-inferior to escitalopram on the primary mood measure at six weeks. Psilocybin performed better on other measures like well-being and sexual dysfunction, suggesting it may offer similar antidepressant benefits without the blunting side effects of SSRIs.

While anecdotal reports suggest benefits, there has never been a proper, controlled, repeated microdosing study of any psychedelic due to regulatory hurdles and high costs. It is plausible that microdosing over a long period might protect against a lowering of mood, but its efficacy in elevating mood in depressed individuals is unknown.