Medical Therapeutic uses for hallucinogens?

[Ryan_m_b]

This thread is a fresh start from a recent one concerning illegal drug use that had to be closed. Its purpose is to discuss the possible role of psychoactive drugs in medical treatment along with the various risks and side effects.

Discussion may be related to illegal recreational drug use, an obviously highly controversial subject in the public sphere with many competing propaganda campaigns. As such strict rules are in place.

Participants may only link to and discuss peer-reviewed papers. No personal beliefs, opinions or anecdotes are allowed. Furthermore what is linked must be the original source i.e. not a news report of a study. Posts that do not comply with this will be deleted. If the thread cannot abide by these rules it will be closed.

This is to encourage a productive, academic discussion. Not a pro/anti drugs flame war.

 

[jackmell]

Here's a few references citing a link between LSD and psilocybin induced psychosis and schizophrenia:

http://www.ncbi.nlm.nih.gov/pubmed/6870484

"The findings supported a model of LSD psychosis as a drug-induced schizophreniform reaction in persons vulnerable to both substance abuse and psychosis."

http://www.ncbi.nlm.nih.gov/pubmed/746371

"LSD was found to produce psychophysiological effects virtually identical to those observed occurring naturally in acute psychotic patients and in normal subjects high in "psychotic" personality traits."

http://journals.lww.com/neuroreport...duces_schizophrenia_like_psychosis_in.24.aspx

"PSILOCYBIN, an indoleamine hallucinogen, produces a psychosis-like syndrome in humans that resembles first episodes of schizophrenia"

http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=5207176

" Schizophrenics who had used drugs experienced the onset of symptoms on average four years earlier than non-users and were also admitted to hospital four years earlier, on average . . . These results are indicative of some precipitating role of drug abuse in the onset of schizophrenia."

http://archpsyc.ama-assn.org/cgi/content/summary/23/2/97

"In recent years we have noted increasingly that psychotic patients come to our attention where no clearly defined acute episode can be specified, but who have allegedly used large doses of psychotomimetic substances over extended periods of time."

In that one "psychotomimetidc" means drugs which cause psychosis symptoms.

 

[dacruick]

While I do not agree that regular LSD has pros that outweigh cons, I will say that our OP might have a point even if he didn't feel like supporting it.

http://www.ncbi.nlm.nih.gov/pubmed/21956378
"A large body of evidence, including longitudinal analyses of personality change, suggests that core personality traits are predominantly stable after age 30. To our knowledge, no study has demonstrated changes in personality in healthy adults after an experimentally manipulated discrete event. Intriguingly, double-blind controlled studies have shown that the classic hallucinogen psilocybin occasions personally and spiritually significant mystical experiences that predict long-term changes in behaviors, attitudes and values. In the present report we assessed the effect of psilocybin on changes in the five broad domains of personality - Neuroticism, Extroversion, Openness, Agreeableness, and Conscientiousness. Consistent with participant claims of hallucinogen-occasioned increases in aesthetic appreciation, imagination, and creativity, we found significant increases in Openness following a high-dose psilocybin session. In participants who had mystical experiences during their psilocybin session, Openness remained significantly higher than baseline more than 1 year after the session. The findings suggest a specific role for psilocybin and mystical-type experiences in adult personality change."

While this study does not explicitly state that "shrooms" are good for you, it does outline possible benefits.

 

[dacruick]

http://journals.lww.com/neuroreport...duces_schizophrenia_like_psychosis_in.24.aspx

"PSILOCYBIN, an indoleamine hallucinogen, produces a psychosis-like syndrome in humans that resembles first episodes of schizophrenia"

That paper you cited is actually a study on schizophrenia not psilocybin. Does temporary schizophrenia constitute as a danger to you? Keeping in mind that the label schizophrenia covers a wide range of psychological experiences. One symptom of schizophrenia is a detachment from reality (http://www.schizophrenia.com/diag.php), which I would say in a temporary setting is not necessarily an intrinsically negative experience.

 

[Evo]

One symptom of schizophrenia is a detachment from reality (http://www.schizophrenia.com/diag.php), which I would say in a temporary setting is not necessarily an intrinsically negative experience.

I read the abstract and it does support what jackmell said. I do not have the entire paper, but it would seem odd that it would contradict the abstract.

Here is a study.

There is, however, evidence that abnormalities in 5-HT2A receptor-dependent neurotransmission may also play a role in some symptoms and cognitive deficits in schizophrenia. Some of this evidence comes from the observation that indoleamine hallucinogens such as LSD or psilocybin can induce—among a wide array of behavioral effects—psychotic symptoms that resemble symptoms of schizophrenia (Vollenweider, 1998; Vollenweider et al, 1998).

A recent study demonstrated that psilocybin not only induced psychotic symptoms, but also impaired spatial working memory in a similar fashion as observed in schizophrenia (Geyer, 1998; Park and Holzman, 1992; Vollenweider et al, 1997, 1998).

http://www.nature.com/npp/journal/v28/n1/full/1300005a.html

 

[dacruick]

Yeah you right. I keep adding references though. Perhaps some of those will better support my claim about the hazards of LSD.

I am partially playing Devil's Advocate here as I do not in any way shape or form recommend the use of LSD. To my knowledge no one has even posted any reliable source that can support a beneficial use of LSD. The link that came under fire was a "Mushroom" link, not LSD. My claim was that there has been at least one study done where controlled use of Psilocybin has shown potentially beneficial effects. I'd be interested in seeing a counter argument outlining how negative psilocybin can be.

 

[dacruick]

"Schizophrenia is often described in terms of positive and negative (or deficit) symptoms.[18] Positive symptoms are those that most individuals do not normally experience but are present in people with schizophrenia"
[18]Sims A. Symptoms in the mind: an introduction to descriptive psychopathology. Philadelphia: W. B. Saunders; 2002. ISBN 0-7020-2627-1.

A friend of mine has Schizophrenia, it is mild, and you would never even know that he had it. My point, that i will repeat, is that saying Psilocybin can induce schizophrenic effects does not mean that those effects are dangerous. If you'd like to make the point that they are dangerous then I'd like you to state specifically which of the symptoms Psilocybin induces, and why (in a temporary and controlled setting) they are harmful.

 

[dacruick]

I keep saying "in a temporary and controlled setting" because no psychedelic is safe in a permanent and/or uncontrolled setting. No one is arguing that recreational uses of psychedelics are safe or beneficial (in a general context). I'm saying that they might have medical uses. For example, the person you know was not in a controlled setting while driving a car...not safe. I don't think it should be legal to use psychedelics outside of a medical facility.

 

[Monique]

I think it is an interesting subject, LSD is indeed subject to clinical investigation for treatment of psychiatric disorders. I'm sure the compound would be chemically modified before it reaches approved-drug status, to achieve the most specific effects (as said, in the current form it can induce psychosis). The zebrafish can be used as a model to dissect those effects http://www.ncbi.nlm.nih.gov/pubmed?term=20561961

This kind of approach would be similar as the use of methamphetamine as a treatment for ADHD. Ritalin (methylphenidate) and Adderall (dexamphetamine) share the mechanism of action and are now approved drugs. The approved drugs lack the high that is associated with methamphetamine.

 

[Monique]

To add to my comments about the application of psychedelic drugs for psychiatric disorders, here is a review published in Nature Neuroscience last year:

After a pause of nearly 40 years in research into the effects of psychedelic drugs, recent advances in our understanding of the neurobiology of psychedelics, such as lysergic acid diethylamide (LSD), psilocybin and ketamine have led to renewed interest in the clinical potential of psychedelics in the treatment of various psychiatric disorders. Recent behavioural and neuroimaging data show that psychedelics modulate neural circuits that have been implicated in mood and affective disorders, and can reduce the clinical symptoms of these disorders. These findings raise the possibility that research into psychedelics might identify novel therapeutic mechanisms and approaches that are based on glutamate-driven neuroplasticity.

paper: http://www.nature.com/nrn/journal/v11/n9/full/nrn2884.html

 

[zoobyshoe]

I can see how my post may have been misinterpreted, but I'd like to again address the ambiguity of the lone term schizophrenia.

"Schizophrenia is often described in terms of positive and negative (or deficit) symptoms.[18] Positive symptoms are those that most individuals do not normally experience but are present in people with schizophrenia"
[18]Sims A. Symptoms in the mind: an introduction to descriptive psychopathology. Philadelphia: W. B. Saunders; 2002. ISBN 0-7020-2627-1.

Just to be clear, you understand that the term "positive" doesn't mean "it's a good thing" here, right? :

Positive symptoms are those that most individuals do not normally experience but are present in people with schizophrenia. They can include delusions, disordered thoughts and speech, and tactile, auditory, visual, olfactory and gustatory hallucinations, typically regarded as manifestations of psychosis.[19] Hallucinations are also typically related to the content of the delusional theme.[20]

http://en.wikipedia.org/wiki/Schizophrenia

 

[rhody]

I had seen a TV documentary awhile ago regarding a close relative of LSD, psilocybin for use in reducing fear and anxiety in advanced stage cancer patients awhile ago.
As luck would have it, I found the original:

http://www.youtube.com/watch?v=-2s9vgAKqFM".

-2s9vgAKqFM[/youtube] [B]Discove...ww.maps.org/news-letters/v06n3/06346hof.html" working for Swiss Pharmaceutical Company Sandoz Labs
[*]looking for a respiratory stimulant, turns to molecule that restricts blood vessels
[*]https://www.google.com/#hl=en&sugex...,cf.osb&fp=2e94b6d9067aa2d7&biw=1680&bih=867", fungus that grows on wild grass
[*]synthesizes an Ergot derivative, lysergic acid with diethylamide
[*]experimenting with the compound five years later drops spilled on his skin, entering his bloodstream
[*]within forty minutes he feels the effects
[*]intrigued he takes a larger dose, on bike ride home, he takes first LSD trip
[*]knew it had a profound mental effect on his consciousness
[*]twenty five micrograms, less than the weight of two salt grains can be enough to feel effects
[*]one ounce is enough to dose three hundred thousand people
[*]Sandoz released thousands of samples under trade name: http://en.wikipedia.org/wiki/Lysergic_acid_diethylamide" , samples sent to worldwide scientists and psychiatrists
[*]by 1965 more than 2000 papers were published and more than 40,000 people experienced its effects
[*]was tested on every major condition for alcoholism to autism
[*]CIA and military experimented to see if it could be used as a covert weapon
[*]by 1970 the FDA categorized it as a class I controlled substance and all experimentation was stopped, claiming there was no medical value in it
[/LIST]

Properties of LSD:

• colorless, orderless, tasteless liquid, mildly bitter solid
• non-addictive
• rapid tolerance with regular use
• cross tolerance between LSD, mescaline, and psilocybin
• a totally pure salt of LSD will emit small flashes of white light when shaken in the dark
• is strongly fluorescent and will glow bluish-white under UV light

Physical Effects:

• dilated pupils
• elevated heart rate
• elevated blood pressure
• increased body temperature

Effects of molecular structure in the brain:

• thought to activate cells in the frontal cortex of the brain
• LSD fits almost like a key into the serotonin receptors
• activates serotonin 2A receptor
• binds to most serotonin receptor subtypes except for 5-HT3 and 5-HT4
• serotonin responsible for relay of signals between brain and nerve cells
• The psychedelic effects of LSD are attributed to its strong partial http://en.wikipedia.org/wiki/Agonist" effects at 5-HT2A receptors
  as specific 5-HT2A agonists (a substance that fully activates the neuronal receptor that it attaches to) are psychedelics
  and largely 5-HT2A specific antagonists block the psychedelic activity of LSD
• perception, emotion, appetite and sleep affected by its fluctuations
• see chemical structure of serotonin versus LSD below

http://img835.imageshack.us/img835/8784/serotoninandlsdmolecule.jpg

Summary of medical applications of hallucinogens:

• treat anxiety in end stage cancer
• treat http://en.wikipedia.org/wiki/Cluster_headache" (2 Bromo)
• used to create and study symptoms of schizophrenia in Lab rats, geneticist, Charles Nichols investigating the genes underlying schizophrenia

Trials in relieving anxiety in advanced stage cancer treatment

• Charles S. Grob, MD, Pilot Study of http://en.wikipedia.org/wiki/Psilocybin"
• twelve adults with advanced-stage cancer and anxiety
• no clinically significant adverse events with psilocybin
• State-Trait Anxiety Inventory trait anxiety subscale demonstrated a significant reduction in anxiety at 1 and 3 months after treatment
• Beck Depression Inventory revealed an improvement of mood that reached significance at 6 months
• established the feasibility and safety of administering moderate doses of psilocybin to patients with advanced-stage cancer and anxiety
• some of the data revealed a positive trend toward improved mood and anxiety
• it is hypothesized that the novelty center in the brain, the http://www.google.com/url?sa=t&rct=...QemZOwCAb5b5wWAQ&sig2=iU2_3i8hbr2rSWJSTaCwqQ" plays a part in helping the patient to remove to clean the slate, removing the anxiety and to see life anew

Trials in treatment of cluster headaches

• Hanover Medical School in Germany, conducted trials in a small sample (6) of patient's who suffer http://www.maps.org/media/view/lsd_alleviates_suicide_headaches"
• administered to each patient three times over a fifteen day period
• for five of the six patients given Bromo (non-psychedelic form of LSD) they
  experienced complete relief from the agonizing pain
• the use of Bromo or LSD is still prohibited even for trials in the US, more good data is needed, a catch 22 situation

Investigation of genes underlying schizophrenic behavior in Lab rats who have been dosed regularly with LSD (28:35 in the video)

• Charles Nichols, geneticist (son of Dr David Nichols) conducts an http://www.ncbi.nlm.nih.gov/pubmed/21352832" of LSD given to rats, why it mimics symptoms of schizophrenia
• given 160 mcgs of the purest LSD once a day for months
• after chronic dosing rats avoid social contact
• reject sugar water, suggesting they no longer seek pleasure
• move fast, startle easily
• became more aggressive
• does the LSD cause schizophrenia, or mimic some of it's effects ?
• if understanding what triggers the onset of schizophrenia, they may be able to design drugs that arrest it

Investigation into why LSD seems to activate all the senses at once

• scientists estimate the human brain perceives 11 million bits of information per second
• conscious mind can only process 200 bits at one time
• brain connects that information to preconceived concepts
• temporarily suspends the brains ability to connect data with preconceived concepts
• the effect is that the drug may de-condition the mind
• filters we normally have to function are lowered, more sensory, emotional and visual impression can be taken in, as well as more access to parts of the mind
• novelty detector in the brain, http://www.google.com/url?sa=t&rct=...QemZOwCAb5b5wWAQ&sig2=iU2_3i8hbr2rSWJSTaCwqQ", use of psychedelics amplify the burst firing of the locus coeruleus in the brain

One piece of the puzzle before I close that I would like more information on is how this serotonin like compound can cross the blood brain barrier, and exist for up to twelve hours binding to the serotonin 2A receptor in the brain. I find it
astounding in the first place that 25 mcg of a dose of this molecule sets off effects for up to twelve hours, and second that only three quarters of one percent of it actually makes it to the brain. Here is http://wiki.answers.com/Q/How_does_LSD_affect_the_brain_and_neurochemistry" .

An interesting side note, only around 3/4 of a percent of lysergic acids (LSA, ALD, LSD, ect.) actually cross the blood-brain barrier.

Does this sound reasonable? If anyone has sources to refute or reinforce this claim, I would be interested to see them. Lastly, does the amount of LSD crossing the blood brain barrier compare to other hallucinogens ?

Rhody...

 

[lisab]

I first heard about this paper on the radio:

http://www.hopkinsmedicine.org/bin/s/m/GriffithsPsilocybin.pdf

At 2 months, the volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed to the experience sustained positive changes in attitudes and behavior consistent with changes rated by community observers.

There was a one-year follow up, discussed here:

http://gazette.jhu.edu/2011/10/31/one-dose-of-hallucinogen-may-create-lasting-personality-changes/

A single high dose of the hallucinogen psilocybin, the active ingredient in so-called “magic mushrooms,” was enough to bring about a measurable personality change lasting at least a year in nearly 60 percent of the 51 participants in a new study, according to the Johns Hopkins researchers who conducted it.

Lasting change was found in the part of the personality known as openness, which includes traits related to imagination, aesthetics, feelings, abstract ideas and general broad-mindedness.

 

[Evo]

Studies on the people that had bad experiences and pyschosis caused by hallucinogens?

I believe highly controlled use of modified LSD that has the hallucinogenic part removed, could have significant benefits.

The part that causes hallucinations seem to cause neurological problems.

http://www.ncbi.nlm.nih.gov/pubmed/12609692

 

[Ms Music]

Sorry, I don't have any peer reviewed papers (and I leave work in 5 minutes) but I will see if I can find some tomorrow. I read this magazine years ago, and thought it might fit into the discussion.

http://www.nationalgeographic.com/adventure/0603/features/peru.html"

I have no idea if any of the information in this article was touched on in Rhody's National Geographic clip, sorry if it is. Native cultures theoretically have used ayahuasca for centuries to treat mental and physical illness. I think it would be very interesting to see if there have been any controlled studies, but as I said, I must leave. I will see what I can drum up tomorrow.

 

[Monique]

I believe highly controlled use of modified LSD that has the hallucinogenic part removed, could have significant benefits.

The part that causes hallucinations seem to cause neurological problems.

http://www.ncbi.nlm.nih.gov/pubmed/12609692

I don't know about that statement, the paper you cite clearly states that the literature is very undefined, the disorder is very rare, and doesn't go into the kind of hallucinations at all. At least the hallucinations that cause negative emotions need to be removed, so far I do agree with you.

 

[Ms Music]

Okay, as promised, I found a study.

http://www.sciencedirect.com/science/article/pii/S0378874107002139

(full pdf found here)
http://www.maps.org/media/ayahuasca-jep.pdf

I found this interesting in Discussions and Conclusions:

These chemical constituents are structurally similar to serotonin and exert an indirect agonist action in the serotonergic system.

But I only read the abstract, introduction, and discussions and conclusions. Not sure what else it gets into.

 

[rhody]

I find it astounding in the first place that 25 mcg of a dose of this molecule sets off effects for up to twelve hours, and second that only three quarters of one percent of it actually makes it to the brain. Here is link.

Rhody...

I haven't spent enough time digging for information on the blood brain barrier, but I plan to in the near future, how and when it was discovered, etc... but I plan to in the near future. I am interested in descriptions, videos of diffusion model studies that involve crossing the blood brain barrier.

I found this interesting, it is short, thought you might like it.

NeuroTrans™ Program: Designed to Deliver Therapeutics Across the Blood-Brain Barrier

Rhody...

 

[rhody]

I stumbled across this while researching something else, which often happens.

Circumventricular organs (CVO) are so named because they are positioned at distinct sites around the margin of the ventricular system of the brain.

They are among the few sites in the brain which have an incomplete blood–brain barrier. As a result, neurons located in circumventricular organs can directly sense the concentrations of various compounds, particularly peptide hormones, in the bloodstream, without the need for specialized transport systems which move those compounds across the blood–brain barrier.

Here are two videos on the lateral ventricular system:

lateral ventrical part 1



lateral ventrical part 2



Do the neurons in the circumventricular organs sense (or process) the concentrations of LSD and if so, do they do it "without the need for specialized transport systems which move those compounds across the blood–brain barrier" ? If so, do they then contribute to the effects that one experiences ? Or must LSD really cross the blood brain barrier in order to produce its effects ?

Rhody... I bet some of you thought I had given up the search into the transport, delivery and absorption of this compound, not a chance...