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InvisibleveggieM

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Can a genetic test predict your response to psychedelic drugs?
    #27295240 - 05/05/21 10:41 AM (4 months, 10 days ago)

Can a genetic test predict your response to psychedelic drugs?
May 5, 2021 - New Atlas

With psychedelic-assisted psychotherapy on the cusp of broad clinical approval in the United States, there is a new pressing need to understand exactly which patients may be best suited to this novel treatment and which patients are most at risk of adverse reactions.

Vancouver-based company Halugen has recently launched a genetic test that purportedly screens for genetic variants influencing how a person may respond to certain psychedelic drugs. But some researchers are skeptical there is any evidence to suggest genetic screening can predict how a person will response to psychedelics.

Set and setting

Back in the 1950s, before LSD crossed over into mainstream recreational circles, a small but dedicated volume of researchers were investigating the therapeutic applications of these weird new drugs called psychedelics. It quickly became apparent to any psychedelic researcher at the time that LSD can generate a huge variety of responses in any given patient. And this was a problem …

Most therapeutic drugs have a consistent and quantifiable effect. Even more intoxicating drugs such as opiates can be dosed with relative predictability. But psychedelics are fundamentally different. Sometimes one could experience a sublime transcendent trip, while other times they could undergo a traumatic hallucinatory nightmare.

If these drugs were going to become effective therapeutic agents it was crucial to understand what factors determine good and bad trips. Those early researchers couldn’t identify any particular physiological factors that seemed to correlate with the quality of a psychedelic experience. By the end of the 1950s most in the field had determined environmental, or extra-pharmacological factors, were the key elements influencing a person's psychedelic trip.

Even a 1958 World Health Organization report on hallucinogens in psychiatry grappled with this problem. Ultimately the WHO report noted how unique these drugs were in the way external factors so fundamentally influence their effects.

“Perhaps their outstanding characteristic is the fluctuating course of their effects, and the striking dependence of these effects on the precise constellation of environmental factors,” the report stated.

All of this coalesced in what is now regarded as the concept of "set and setting". Popularized by Timothy Leary in the 1960s, this hypothesis posits an individual’s response to a psychedelic drug is primarily shaped by, “set (personality, preparation, expectation, and intention of the person having the experience) and setting (the physical, social, and cultural environment in which the experience takes place).”

Fast forward to 2021, psychedelic-assisted psychotherapy is finally back in the mainstream and on the verge of being rolled out in thousands of clinics across North America. And the same questions that were raised over 60 years ago are again being asked.

So what factors can be used to minimize the risk of a negative psychedelic experience in a therapeutic context?

"Our ability to predict is almost none at all”

In a recent 60 Minutes profile on the modern renaissance of psychedelic science, Anderson Cooper asked pioneering researcher Roland Griffiths if there is any way to predict which patients could have a bad psychedelic experience. Griffiths swiftly responded, “Our ability to predict that is almost none at all.”

Over the last decade hundreds of people have been administered psilocybin as part of clinical trials exploring psychedelic-assisted psychotherapy. A number of safety guidelines have been clearly established to help inform participant selection in trials. And so far, these measures have worked pretty well with nearly no serious adverse events reported in trials testing psychedelic therapies.

Most current screening measures for psychedelic clinical trials look to exclude individuals with either a personal, or familial, history of psychiatric illness (primarily schizophrenia, psychosis or bipolar disorder). Subjects with hypertension can also sometimes be excluded, as well as those on certain kinds of antidepressants.

That's about it. Psychedelics have proven to be extraordinarily safe drugs when administered in controlled conditions. But a few thousand patients dosed in clinical trials is one thing, potentially millions of people dosed once the treatments become widely available is a whole different game.

The psychedelic genetic test

Vancouver-based start-up HaluGen Life Sciences is pursuing a way to use modern genetic technology to help offer clinicians a quantifiable way to evaluate how a patient could respond to psychedelic drugs. Early in 2021 the company released the first iteration of its novel psychedelic genetic test.

For CAD$89 HaluGen offers a personalized psychedelic report incorporating a number of surveys and questionnaires with genetic test tracking five specific gene variants. The report is supplied through, of course, a custom-made smartphone app.

“The HaluGen psychedelic pre-screening platform offers a comprehensive solution to identify inter-individual variations to psychedelic drug effects, highlight short- and long-term genetic risk profiles as well as categorize personal and familial risk,” the company states. “By combining a simple, non-invasive cheek swab DNA sample with comprehensive pre- and post-psychedelic usage questionnaires, HaluGen offers a simple and effective method for users, researchers and clinicians to gain further insights into their psychedelic experience.”

Out of the five gene variants screened in HaluGen’s test, three target one’s propensity for developing mental health disorders including schizophrenia and psychosis, one tracks a gene variant claimed to influence ketamine metabolism, and another looks for a gene variant thought to influence serotonin receptor density.

It is this last genetic target that forms the company’s "Classical Psychedelic Report", predicting a “person’s sensitivity to serotonergic psychedelics such as LSD, DMT and psilocybin.”

So what evidence is there that specific genetic variants in the serotonin-2A receptor gene can influence a person’s sensitivity to psychedelics? Little scientific data is presented on the company’s website and in response to a query from New Atlas HaluGen cited this specific 2019 study.

The study is a small but robust and influential brain imaging study investigating exactly how psilocybin could be exerting its hallucinogenic effects on the brain. Building on prior research suggesting “serotonergic psychedelics exert their psychoactive effects through the serotonin 2A receptor,” the study offers strong evidence that psilocybin does indeed exert its subjective psychedelic effect by stimulating serotonin 2A receptors.

However, the study offers no direct evidence of certain genetic variants influencing subjective psychedelic responses.

Jacob Aday, a researcher from Central Michigan University, recently published a systematic review of the current literature on the factors that can predict a response to psychedelic drugs. In a statement to New Atlas, Aday expresses skepticism that a genetic test such as this could offer any robust prediction of psychedelic responses.

“To date, there has been no peer-reviewed research identifying genes that can be used to predict how individuals will react to psychedelics,” Aday tells New Atlas. “Our team just completed a rigorous systematic search of the psychedelic literature and no such study has been published. Therefore, I am skeptical about claims that genetics can be used to robustly predict psychedelic effects.”

In a White Paper supplied to New Atlas by HaluGen, the company describes individuals with a particular HTR2A gene variant as likely having high serotonin 2A receptor density.
“Therefore, HTR2A TT (AA) carriers with higher 5-HTR2A receptor density, could be more susceptible to stronger hallucinogenic effects through increased receptor activity and may wish to consider a lower starting dose when undergoing potential psychedelic therapy,” states HaluGen.

In direct response to this quote Aday says, “…there are no studies showing this to be the case and it could in fact be the complete opposite—that those with high 5-HT2A receptor density would need a higher dosage to effectively stimulate their high number of receptors.”

Somewhat recalling the older "set and setting" hypothesis, Aday’s recent review article on the subject homed in on certain personality traits that seem to best predict an individual’s acute response to psychedelic drugs. The review article, co-authored with Alan Davis from The Ohio State University and colleagues from Central Michigan University, found absorption, openness, and acceptance to be the three traits most likely to lead to a positive psychedelic experience.

The article found individuals low in those specific traits were more likely to suffer adverse or negative psychedelic experiences. Those in apprehensive, preoccupied or confused states also displayed greater adverse responses to psychedelics.

"There was also tentative evidence that increased experience with psychedelics and increased age were associated with slightly less intense effects with the drugs," notes Aday. "And there weren't any differences according to sex. Men and women responded similarly."

Ultimately it is unclear exactly how robust genetic screening for psychedelic effects is right now. Aday says there isn’t enough direct evidence to show genetics can predict an individual’s reaction to psychedelics. He does suggest, on the other hand, is that there is enough evidence to establish how baseline personality traits can influence a psychedelic experience.

Just like we have decades of strong research investigating how set and setting influences a psychedelic experience, we have good evidence pointing to specific personality traits that can be associated with beneficial psychedelic effects.

And … we can screen for those traits using conventional pre-existing techniques, including interviewing subjects before dosage sessions and closely tracking family histories of schizophrenia or psychosis. While the HaluGen test includes surveys and questionnaires that may lend themselves towards this approach, a lack of evidence at this stage raises doubts over the veracity of genetic testing.

Speaking recently to Forbes Albert Garcia-Romeu, a researcher from Johns Hopkins who has worked with patients on early psychedelic clinical trials, agrees it may be more useful right now to screen for familial mental health conditions.

“I don't think we know enough yet to use that in a way that would work properly,” says Garcia-Romeu. “You can, I think, get the same type of information just by looking at a person's mental health and family mental health history. And it's probably more relevant to do that than the genetic work.”

In the future there certainly may be stronger evidence of genetic characteristics that influence the acute effects of psychedelic drugs. But right now Aday says we should focus more on what we actually have good evidence for.

"The genes [HaluGen] selected to screen for they chose because they are associated with traits that are thought to be predictive of acute effects,” says Aday. “However, it would be much more efficient to just screen for those traits in the first place rather than for genes that are weakly linked to those traits. They are essentially diluting their predictive power by examining variables that are indirectly linked to psychedelic effects.”


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InvisibleHolybullshit
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Re: Can a genetic test predict your response to psychedelic drugs? [Re: veggie]
    #27295255 - 05/05/21 10:47 AM (4 months, 10 days ago)

The results of that $89 test seem pretty....useless.

I guess for young people, or people who are psychedelic naive. Personally I just didn't see any information pop out at me that seemed worth spending ninety dollars, let alone going through the trouble.


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OfflineReynardTheFox
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Re: Can a genetic test predict your response to psychedelic drugs? [Re: Holybullshit]
    #27295394 - 05/05/21 01:11 PM (4 months, 10 days ago)

The complete lack of evidence for their claim makes it literally bogus. This is tantamount to a scam.


--------------------
"Every actual State is corrupt. Good men must not obey laws too well" - Ralph Waldo Emerson

"If I am the devil's child, I will live then, by the devil" - Ralph Waldo Emerson


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Offlinesonoramo
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Re: Can a genetic test predict your response to psychedelic drugs? [Re: Holybullshit]
    #27295483 - 05/05/21 02:40 PM (4 months, 10 days ago)

Quote:

Holybullshit said:
The results of that $89 test seem pretty....useless...




The obvious alternative is to give the client a moderate dose, watch closely and see what happens. But at $89, the genetic test may be cheaper than paying a trained therapist to sit through a low dose session where very little happens.

To me, this points to how "medicalization" gets on a crazy-wrong track, compared with just giving people flight instructions and access to the medicine. If they aren't paying a therapist and billing insurance and there's no potential for malpractice lawsuits, starting low and then continuing with full dosage is practical and affordable. And probably not accessible in the medicalized insurance-reimbursement model.


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OfflineVP123
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Re: Can a genetic test predict your response to psychedelic drugs? [Re: veggie]
    #27295671 - 05/05/21 05:14 PM (4 months, 10 days ago)

Quote:

veggie said:
Can a genetic test predict your response to psychedelic drugs?


It seems that the answer is NO.


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Offlinesonoramo
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Re: Can a genetic test predict your response to psychedelic drugs? [Re: VP123]
    #27295773 - 05/05/21 06:24 PM (4 months, 10 days ago)

Quote:

VP123 said:
Quote:

veggie said:
Can a genetic test predict your response to psychedelic drugs?


It seems that the answer is NO.




Although "no" is more likely than "yes," but I wouldn't underline and bold that "no."


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Invisiblebadchad
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Registered: 03/02/05
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Re: Can a genetic test predict your response to psychedelic drugs? [Re: sonoramo]
    #27296774 - 05/06/21 11:02 AM (4 months, 9 days ago)

Quote:

sonoramo said:


The obvious alternative is to give the client a moderate dose, watch closely and see what happens.




The challenge here is that there is large variability in experiences.  Even if you give a subject an identical dose twice, the sessions can be very different.  Given this variability, I'm skeptical this test predicts anything.


--------------------
...the whole experience is (and is as) a profound piece of knowledge.  It is an indellible experience; it is forever known.  I have known myself in a way I doubt I would have ever occurred except as it did.

Smith, P.  Bull. Menninger Clinic (1959) 23:20-27; p. 27.

...most subjects find the experience valuable, some find it frightening, and many say that is it uniquely lovely.

Osmond, H.  Annals, NY Acad Science (1957) 66:418-434; p.436


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Offlinedurian_2008
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Re: Can a genetic test predict your response to psychedelic drugs? [Re: badchad]
    #27297090 - 05/06/21 04:10 PM (4 months, 9 days ago)

The warrior gene(s) appear to be named after monoamine oxidase?
Quote:

What is the normal function of the MAOA gene? This gene is one of two neighboring gene family members that encode mitochondrial enzymes which catalyze the oxidative deamination of amines, such as dopamine, norepinephrine, and serotonin.




Quote:

5-HT is short for 5-hydroxy-tryptamine, which is serotonin.




No one genetic test could predict all the possible responses.

I have apparently gotten involved in some trendy way to waste money. :awesomenod:

But, if you already have ancestry tests (the more markers the better) the raw data can be plugged into livewello (and probably others) for about half the price, and you can run lots and lots of these tests on yourself, if you have an autistic obsession with numbers. I just did "HTR2A Serotonin Pathway" for free.

I originally ran some of these on myself as a joke, having heard how certain tribal groups were predisposed to crime. Gattaca won't like me. :shrug:


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OfflineVP123
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Re: Can a genetic test predict your response to psychedelic drugs? [Re: sonoramo]
    #27298449 - 05/07/21 12:04 PM (4 months, 8 days ago)

Quote:

sonoramo said:
Quote:

VP123 said:
Quote:

veggie said:
Can a genetic test predict your response to psychedelic drugs?


It seems that the answer is NO.




Although "no" is more likely than "yes," but I wouldn't underline and bold that "no."




Yeah, that was a bold move on my side (pun intended). But I still don't think the genetic test they are proposing will answer the question. People tend to overestimate the usefulness of a genetic test. To put it this way, If I was born with the genes that would make me an Olympic athlete but I only sit down in front of the TV while snacking, I will never be even close to be considered physically fit. In fact, even exercising regularly would not make me and Olympic athlete. You have to really beat your ass in the gym and the track, have the right coaches and training program, compete against other elite athletes regularly, have the right nutrition, etc. This is a very common problem, when there are so many variables influencing an outcome, it is an error to try to simplify it to one single variable (genetics in this case).


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InvisibleHolybullshit
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Re: Can a genetic test predict your response to psychedelic drugs? [Re: sonoramo]
    #27299900 - 05/08/21 11:04 AM (4 months, 7 days ago)

Quote:

sonoramo said:
Quote:

Holybullshit said:
The results of that $89 test seem pretty....useless...




The obvious alternative is to give the client a moderate dose, watch closely and see what happens. But at $89, the genetic test may be cheaper than paying a trained therapist to sit through a low dose session where very little happens.

To me, this points to how "medicalization" gets on a crazy-wrong track, compared with just giving people flight instructions and access to the medicine. If they aren't paying a therapist and billing insurance and there's no potential for malpractice lawsuits, starting low and then continuing with full dosage is practical and affordable. And probably not accessible in the medicalized insurance-reimbursement model.




Even with the test, I can't see that changing anything in practice...maybe one day in the future testing could get to that point, but not this. All it could do is ease patient concerns, or it could aggravate them for what in reality is no reason at all.


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Offlinedurian_2008
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Re: Can a genetic test predict your response to psychedelic drugs? [Re: Holybullshit]
    #27301681 - 05/09/21 04:14 PM (4 months, 6 days ago)

Lots of receptors implies the strongest response.

I think, the tests come with emotional baggage.

If it says, you do not respond to negative reinforcement, this can be called a kind of endurance or retardation or forgiveness. One of my services regards it as learning impediment. I heard of a tribe that died out, when needful resources were just up a hill. 

If it says, you have a strong response to whatever substance (maybe unpleasant) it says, a likelihood of dependence.

Objective data is always subject to personal interpretation.


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