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Published: 04 October 2023

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Vaping renders immune cells unable to move to meet threats

Even moderate exposure to nicotine-free vapour causes suppression of neutrophil’s typical activity.

Inhaling vapour from an e-cigarette may be stopping frontline immune cells from working typically, as a new study shows that even moderate smoke exposure suppresses cell activity. 

The findings are published in the Journal of Allergy and Clinical Immunology and suggest that inhaling e-cigarette smoke could be damaging neutrophils, the first line of defence the human immune system has. The findings are important as previous research has shown that damage caused to neutrophil by cigarette smoking can lead to long-term lung damage.

Researchers from the University of Birmingham took blood samples from healthy donors who had never smoked or vaped. The team then exposed neutrophils taken from the blood to 40 puffs of unflavoured vape, which previous studies have shown is a low daily exposure; with half of the samples were exposed to nicotine-containing vapour while the rest to nicotine-free alternatives.

E-cigarettes are a proven, lower-harm, tool to help smokers quit smoking but our data adds to current evidence that e-cigarettes are not harmless and highlights the need to fund longer-term studies in vapers.

Dr Aaron Scott, Associate Professor in Respiratory Science at the University of Birmingham

Results of the tests showed that in both the nicotine and non-nicotine groups, the neutrophils remained alive but were stuck in place, rendering them incapable of effectively tackling threats to the body.

Further experiments with neutrophils exposed to e-cigarette vapour suggest a build-up of a microfilament within the cells which are unable to re-arrange themselves properly is driving the suppression of the cells normal function. 

Actin is usually found as small filaments within cells and rearrange themselves into a network to help a cell change its shape. This function is used by neutrophils so that they can move towards and surround threats to destroy them. 

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Published: 30 August 2023

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Abstract: Research in the last decade has expressed considerable optimism about the clinical potential of psychedelics for the treatment of mental disorders. This optimism is reflected in an increase in research papers, investments by pharmaceutical companies, patents, media coverage, as well as political and legislative changes. However, psychedelic science is facing serious challenges that threaten the validity of core findings and raise doubt regarding clinical efficacy and safety. In this paper, we introduce the 10 most pressing challenges, grouped into easy, moderate, and hard problems. We show how these problems threaten internal validity (treatment effects are due to factors unrelated to the treatment), external validity (lack of generalizability), construct validity (unclear working mechanism) or statistical conclusion validity (conclusions do not follow from the data and methods). These problems tend to co-occur in psychedelic studies, limiting conclusions that can be drawn about the safety and efficacy of psychedelic therapy. We provide a roadmap for tackling these challenges and share a checklist that researchers, journalists, funders, policy makers, and other stakeholders can use to assess the quality of psychedelic science. Addressing today’s problems is necessary to find out whether the optimism regarding the therapeutic potential of psychedelics has been warranted and to avoid history repeating itself.

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Published: 23 August 2023

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As the medicinal use of psychedelics gains mainstream attention, fears remain over their effect on mental health and the need for safe administration

Guardian’s David Cox 19 Aug 2023 

In June 2021, 32-year-old actor Kate Hyatt travelled to a farmhouse near Great Malvern in Worcerstershire for a plant medicine retreat that she hoped would improve her mental health after a difficult time during the pandemic lockdowns. While there, she is believed to have taken a substance called wachuma, or San Pedro cactus, a powerful hallucinogen used by Indigenous people in the Andes for thousands of years.

But Hyatt did not experience relief; instead, her mental health worsened. Three months later, she described being in “some sort of psychotic break” and feeling as if her brain was going to explode. Later that autumn she took her own life. At the subsequent inquest, the coroner’s report linked her worsening symptoms to the hallucinogens she had consumed.

Such tragedies represent the darker side of the psychedelics renaissance. These cases are often forgotten amid the feverish anticipation surrounding the therapeutic potential of these drugs, combined with exhaustive media coverage, the rapid rise of a billion-dollar industry – ranging from venture capital-backed startups to wellness retreats – and the hype around last year’s Netflix series How to Change Your Mind (based on Michael Pollan’s bestselling book).

Self-medication is a particular concern, encouraged by the relentless promotion of the possible benefits of psychedelics

Yet without careful monitoring and scrutiny of who receives them, this class of drugs – which includes LSD, MDMA (commonly known as ecstasy or molly) and psilocybin (the active ingredient of magic mushrooms) – can be dangerous. There is evidence that they can destabilise vulnerable individuals who have experienced a previous psychotic episode or have a family history of psychosis.

“Psilocybin affects serotonin and it’s been known for some time that drugs which do this can set off a manic episode in people with bipolar disorder,” says Andrew Penn, a psychedelics researcher at the University of California, San Francisco. “What we worry about with somebody with underlying psychotic illnesses is that the drug might wear off, but the illness symptoms persist, or even that the drug has helped them emerge.”

Self-medication is a particular concern, encouraged by the relentless promotion of the possible benefits of psychedelics. While clinical studies will use precisely controlled doses and patients will be supervised by trained staff, this does not necessarily happen when people take psychedelics alone or at retreats. “People using it out there in the wild, as we say – that’s rapidly increasing,” says Haley Dourron, a researcher at the University of Alabama at Birmingham. “We’re seeing more instances of people having bad experiences, especially those with questionable mental health histories, or use in unsafe circumstances.”

When Compass Pathways, a London-based biotechology company, published the results of a phase 2b trial of psilocybin for treatment-resistant depression, it reported that three patients demonstrated suicidal behaviour for at least a month after receiving the drug.

Penn has heard first-hand how tragedy can happen when the drug is taken in the wrong settings. “One recent case was very concerning,” he says. “A 21-year-old woman tried to treat her own depression through self-medicating with a high dose of psilocybin. She got very distressed, and apparently tried to go to the office the next day before deciding she wasn’t in a fit state to work. She turned around, stopped in the middle of the Golden Gate Bridge [in San Francisco] and jumped off.”

While independent researchers are optimistic, they still urge caution. Dourron feels that there needs to be a more concerted scientific effort to look for potential risks in the wider population, particularly in vulnerable patients.

Matt Butler, an academic psychiatrist at King’s College London, is concerned that the substantial commercial interest in psychedelics will lead to them being ushered into the mainstream prematurely.

“There are pressures to get things pushed forward,” he says. “The results are promising, but I think we need to do more research. There are lessons from the 50s, 60s and 70s, when psychedelics were pushed through quite quickly and things didn’t end well.”

The placebo problem

The psychedelics revolution is progressing at pace. Regulators in Australia gave psychiatrists the green light from last month to prescribe MDMA and psilocybin for PTSD and depression.

“Maybe it’s a decision based on their perceived lack of risk versus the potential for usefulness,” says Rachael Sumner, a pharmacy researcher at the University of Auckland in New Zealand. “But there are these issues that are well known.”

Sumner’s surprise stems from the question marks that still exist regarding how to measure the benefits of psychedelic-assisted treatment. Most medicines are assessed by giving one group of patients the active drug and another a placebo, before comparing the two. Ascertaining whether a new drug performs better than a placebo is particularly imperative in depression, where patients commonly experience a short-term psychological boost from receiving a new treatment.

But this works only if patients cannot guess whether they have received the drug or not, and with psychedelics, most can tell. While scientists have tried various placebos – from the vitamin supplement niacin, which causes flushes, to the sedative remifentanil – Sumner says that in her experience the majority of participants can guess.

This can cause an additional problem. The crushing disappointment from realising they have not received the psychedelic can cause a patient’s condition to deteriorate. Both Butler and Sumner have published papers speculating that some of the large differences between psychedelic and placebo groups in trials is not just because patients on the drugs have improved, but because those on the placebo have worsened. “I think we’re probably overestimating how effective they are at the moment,” says Butler.

“In the media, a lot of ink gets thrown about this topic,” he says. “People read that and say: ‘I have depression and my buddy grows mushrooms. Maybe I’ll just take this and see if it makes me better.’ But what those narratives are overlooking is that there’s a lot more to psychedelic treatment than just the drug, and there’s this whole context and safety container that makes it safer.”

(For complete article Is the therapeutic potential of hallucinogens risky and overhyped? | The Guardian)

Also see Psychedelics: The New Panacea – Just Like Cannabis, it will Fix Everything, Won’t it?

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Published: 20 June 2023

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Links between sexual violence incidence rates and alcohol consumption or the use of drugs, are highlighted in new research on first year college students.

• One in three (35pc) women who experienced sexual violence said incapacitation by alcohol or drugs was the tactic used by the perpetrator.
• [Substance assisted] Coercion (34pc) and force or threat of force experienced by 20pc of women.
• Men experienced sexual violence at lower rate of 18pc saying incapacitation due to alcohol/drugs was a tactic, with by 16pc citing coercion and 8pc, force or threat of force.
• Two in three (65pc) of females in the survey and 72pc of males had what was regarded as a “hazardous pattern of alcohol consumption”.
• Among females, the experience of completed non-consensual penetration was above 35pc for those who used alcohol at a hazardous level and those who had used cannabis in the past 12 months.
• It rose to 44pc among females who had used ecstasy and 48pc among those who had used cocaine or ketamine.
• For male students, the experience of non-consensual penetration was particularly associated with having used drugs in the past 12 months

(Source: Links between sexual violence and alcohol or drug use highlighted in new student study )

Also see The ‘Unleashing’ Of Domestic, Familial & Intimate Partner Violence – The Drug Factor.