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RESOURCES:
Scientific studies on Hallucinogens relevant to Ballot Question 4
This page provides links to public data or scientific articles on the many known harms and limited known benefits of hallucinogens.
HARMS
Harms of hallucinogens fall under three categories: Harm to the public, and harm to patients with mental illnesses, and harm to others who take hallucinogens.
Public health harms:
More emergency room visits and burdening overcrowded hospitals
Emergency room visits have increased over 50% with hallucinogens in California
https://pubmed.ncbi.nlm.nih.gov/38213013.
More car accidents and direct harm to the public
According to Massachusetts data license revocations for OUI, drugs are up 65 percent in the last three years. https://www.nbcboston.com/news/local/high-behind-the-wheel-officers-lack-training-to-spot-drugged-drivers/127832/
Between 2020 and 2021, there was a significant increase in the number of drivers with BAC .08+ involved in fatal crashes. Unfortunately, several states had substantial jumps. Alaska saw a 100% increase, while the District of Columbia, Idaho, Massachusetts, and Delaware all recorded increases above 50%.
https://www.safehome.org/resources/dui-statistics.
9% of all hallucinogen users drove under the influence of hallucinogens in the past year. Among regular users, over 30% drove under the influence of hallucinogens in the past year.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8595810/
Experience with cannabis, which is much less potent than Ballot Question 4 hallucinogens (mescaline, DMT, psilocybin, psilocyn, ibogaine):
This 2022 study of 11 Western US states finds some variability, but overall 2% increase in fatal crashes and 6% increase of overall car accidents after cannabis legalization.
https://pubmed.ncbi.nlm.nih.gov/35838426/
This study found that 18% of car accidents involved cannabis after legalization. Alcohol remains a problem as well.
https://www.sciencedirect.com/science/article/abs/pii/S0022437521001675
Fatal crashes increased in two states after commercialization
https://www.sciencedirect.com/science/article/abs/pii/S0001457519310267
Harms to people with mental illnesses:
European emergency room visits are quantified for hallucinogens causing psychosis: about 20% of those exposed to psilocybin who come to ERs are psychotic
https://link.springer.com/article/10.1186/s12888-016-1002-7
MDMA causes persistent long-term psychosis in 25% of persons (This is not in the ballot question but is the drug studied and rejected recently by FDA for PTSD):
https://www.tandfonline.com/doi/full/10.1080/10826084.2018.1521430?
LSD has the same basic mechanism as psilocybin and DMT but is more potent. It causes psychosis so clearly that it is used a basic animal model to create psychosis.
https://www.mdpi.com/1422-0067/17/11/1953
There are many case reports of patients with bipolar illness or schizophrenia that have gotten more psychotic on these agents, but no large studies mainly because it would be considered unethical to give drugs which cause psychosis to persons with psychotic diseases.
Harms to those who take hallucinogens
Psilocybin can make normal people psychotic at least temporarily
https://journals.lww.com/neuroreport/fulltext/1998/12010/psilocybin_induces_schizophrenia_like_psychosis_in.24.aspx
Hallucinogens can be addictive, despite absence of physical dependence or withdrawal
“Addiction” is a psychological concept: someone takes something and keeps taking it and has difficulty stopping taking it. It is not a “physiological” concept, often called “physical dependence”: there does not have to be biological “tolerance” (meaning you have to take more of the substance to get the same effect) or “withdrawal” (meaning you have physical symptoms, like stomach aches or pains, when you stop the substance).
You can have addiction with the physiological aspects of tolerance and withdrawal – as with alcohol and opiates – or you can have addiction without much in the way of physiological tolerance and withdrawal – as with cocaine and amphetamines and marijuana. Psychedelics like ketamine and psilocybin are in the latter category.
You also can have physiological aspects like withdrawal without psychological addiction – as with serotonin reuptake inhibitor (SRI) antidepressants, which have a severe withdrawal syndrome but are not psychologically addictive.
In sum: absence of physical dependence does not mean a substance is not addictive; and presence of physical dependence does not mean a substance is addictive.
This NIH report and webMD summary below are examples of how my perspective is widely held in the medical community, as also with the Lancet article.
https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(23)00230-4/fulltext
https://www.ncbi.nlm.nih.gov/books/NBK20368/
https://www.webmd.com/mental-health/addiction/tolerance-dependence-addiction-explained
Studies that provide evidence for hallucinogen addiction:
11% of college students abuse hallucinogens along with other drugs of abuse. They are not recovering from their addiction by using hallucinogens, but rather taking these drugs of abuse with other drugs of abuse.
https://www.sciencedirect.com/science/article/pii/S2352853219301804
16% of hallucinogen users meet criteria for substance abuse:
https://www.tandfonline.com/doi/abs/10.1080/10550490802269064
This issue has been known and debated since 1965
https://jamanetwork.com/journals/jama/article-abstract/654517
Clinicians see psychological dependence (addiction) with these drugs
https://www.tandfonline.com/doi/abs/10.1300/J029v15n01_03
About 25% of adolescents who take hallucinogens are addicted to them
https://www.sciencedirect.com/science/article/abs/pii/S0376871609001550
Hallucinogen users tend to abuse other substances, with a five fold increased rate of heroin abuse:
https://www.sciencedirect.com/science/article/abs/pii/S0306460318305355
LIMITED KNOWN BENEFITS
Studies are all short-term, showing temporary symptom improvement, not long-term change in disease course.
The MAPS PTSD study that was taken to FDA, and rejected for marketing indication, was 18 weeks long. It showed MDMA better than placebo for short-term PTSD symptoms. Some papers were retracted by journals because of concerns about data integrity and ethical conduct.
https://www.nature.com/articles/s41591-023-02565-4
No psychedelic has been compared to standard psychiatric medications for PTSD, and thus not proven more effective.
The longest antidepressant randomized clinical trial is 6 weeks. Longer reports are not randomized.
Hallucinogens are not more effective than standard antidepressants for depression.
Psilocybin was not more effective than escitalopram in a 6 week RCT: NEJM 2021
Trial of Psilocybin versus Escitalopram for Depression | New England Journal of Medicine (nejm.org)
Just published in September 2024: At 6 month continued observational – not randomized - follow-up, psilocybin still was not better for depressive symptoms, which was the primary outcome, though it had some benefits on secondary outcomes of quality of life
Effect of psilocybin versus escitalopram on depression symptom severity in patients with moderate-to-severe major depressive disorder: observational 6-month follow-up of a phase 2, double-blind, randomized, controlled trial - eClinicalMedicine (thelancet.com)
A new recent network meta-analysis compared psychedelics to antidepressants in depression and showed that they are not proven better: It found that high dose psilocybin is only marginally better than a standard antidepressant (escitalopram) in these trials. And low dose psilocybin, which is equivalent to the current ballot question, is not any better than the standard antidepressant for short-term depression symptom improvement, contrary to claims of the psychedelic advocates. The study addresses the observation that the placebo response is small in psychedelic studies, compared to the placebo response in standard antidepressant studies. This is because psychedelics have such obvious hallucinatory effects that patients can tell whether they receive them or not. So the fair comparison would be to placebo effects in other studies of depression.
On figure 2, if you look at low dose psilocybin compared to placebo response in antidepressant trials, the benefit with low dose psilocybin is 2.15 points on the depression rating scale. A 3 point difference is the minimum that is the standard for a clinically meaningful difference (though it is still small); this is the standard also for a claim for FDA approval. The 2 point difference is smaller and the confidence intervals include the null value (-2.01, 6.13), which means that there is no statistical significance and the actual difference could very well be nothing.
New study provides further support for psilocybin’s potential to treat depressive symptoms. News release. BMJ Group; August 21, 2024. Accessed September 30, 2024.
Hsu TW, Tsai CK, Kao YC, et al. Comparative oral monotherapy of psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, ayahuasca, and escitalopram for depressive symptoms: systematic review and Bayesian network meta-analysis. BMJ. 2024;386:e078607. doi:10.1136/bmj-2023-078607
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