182 - Psychedelics & Recreational Drugs

KEYPOINTS

• 01

  Drug harms can be scored on 16 dimensions.

  Nutt, professor of neuropsychopharmacology at Imperial College London, began working on principles for assessing drug harms in the 1990s and advised the UK government from 1994. His framework rates nine harms to the user and seven to society. Across Europe, Britain and Australia, the most harmful drug overall is consistently alcohol — chiefly because of harms to others and because about 80% of American and British adults drink.

• 02

  Alcohol is uniquely dangerous because it combines acute and chronic toxicity.

  Tobacco kills more people, but usually in their 50s and 60s and with purely chronic toxicity; alcohol kills people in their 20s through accidents and acute poisoning too. Nutt says there's no healthy dose of alcohol, though some doses may not rise to meaningful toxicity; Attia notes how easily the line is crossed.

• 03

  US politics shaped global drug law.

  Nutt says every British drug law until 2016 was made at the behest of the Americans, starting with 1934-era policy, and the UN largely follows US direction. He traces cannabis hostility to Harry Anslinger's efforts to keep his bureau relevant after alcohol prohibition ended — nearly 90 years of disinformation.

• 04

  The cannabis research gap leaves basic questions unanswered.

  Attia is frustrated he can't tell parents whether a 16-year-old smoking pot will harm brain development. Nutt argues that with tens of millions of users, utility and harms could have been mapped within a few years if research had been permitted.

• 05

  Fentanyl is an economic inevitability of supply crackdowns.

  When heroin supply was squeezed, Mexican cartels turned to fentanyl, roughly 50 times more potent than heroin and about half the cost to make. Nutt favours studying treatments like ibogaine for opioid addiction, though its cardiac risks make research difficult; Attia notes untreated opioid addiction itself might carry something like 300-per-1,000 mortality.

• 06

  Psychedelics may work by disrupting the default mode network.

  Nutt's team's thinking is that the psychedelic state profoundly disrupts the brain's default mode network, potentially breaking over-learned habit circuits in addiction and depression and letting people escape rigid patterns.

• 07

  LSD research was extensive and largely positive before it was banned.

  Synthesized in the late 1930s, LSD was the subject of over 130 NIH-funded grants, about 40,000 patients and 1,000 papers; it appeared safe, didn't cause psychosis, and if anything reduced suicide. Therapeutic 'big trip' doses were around 100–125 micrograms; 25 micrograms was used to lower resistance in psychotherapy, and anything over about 10 micrograms is perceptible.

• 08

  The ban may have cost far more lives than it saved.

  A modern meta-analysis by two Norwegian researchers of six old US trials of one or two LSD doses for alcoholism found an effect size of about one — twice that of any later treatment. Nutt estimates over 100 million people died prematurely from alcohol in the 50 years since; even 10% helped would be 10 million lives, versus perhaps 2,500 saved by the ban. This is his rough calculation.

• 09

  Psychedelics show rapid tolerance.

  Take LSD daily and the second dose is far weaker; at some point people stop responding — unlike drugs such as acetaminophen, whose effect stays roughly constant.

• 10

  Psilocybin vs. escitalopram for depression.

  In Nutt's New England Journal of Medicine trial, all patients received the same psychotherapy; one arm got 25 mg psilocybin (two doses about three weeks apart), the other escitalopram (Lexapro) with a 1 mg psilocybin placebo. It was reported as a negative study on its primary measure; Nutt says it was never powered for non-inferiority, which would need about 150 patients per arm. 25 mg of psilocybin roughly equals 4–5 g of dried mushrooms.

• 11

  Ketamine was the first new antidepressant breakthrough in decades.

  Couldn't be patented, so esketamine was developed. Depression doses are modest, but recreational users escalate to grams a day.