Psychedelics and schizophrenia

[Gradient]

Article Published: April 2009


This is a really fantastic, concise article. One of the best I've found to date with great diagrams for many of the most commonly ingested psychedelics. It even goes so far as to discuss the genetic components of Schizophrenia - which is extremely new research. Abstract:

Research on psychedelics such as lysergic acid diethylamide (LSD) and dissociative drugs such as phencyclidine (PCP) and the symptoms, neurochemical abnormalities and treatment of schizophrenia have converged. The effects of hallucinogenic drugs resemble some of the core symptoms of schizophrenia. Some atypical antipsychotic drugs were identified by their high affinity for serotonin 5-HT(2A) receptors, which is also the target of LSD-like drugs. Several effects of PCP-like drugs are strongly affected by both 5-HT(2A) and metabotropic glutamate 2/3 receptor modulation. A serotonin-glutamate receptor complex in cortical pyramidal neurons has been identified that might be the target both of psychedelics and the atypical and glutamate classes of antipsychotic drugs. Recent results on the receptor, signalling and circuit mechanisms underlying the response to psychedelic and antipsychotic drugs might lead to unification of the serotonin and glutamate neurochemical hypotheses of schizophrenia.

Reputation Comments on this post:

	Thanks for the interesting study!
	Great post!
	interesting point

[eche05]

I just wrote a paper on that a few days ago for a psychiatry/pharmacology lecture(er). One of my favorite subjects, i'll save the troubles of complication by giving a general overview


Schizophrenics generally have:

A.) Abnormally high levels of dopamine (specifically dopamine-4 and 2)
B.) Generally low serotonin (accross the spectrum)
C.) High ammounts of norepinephrine (overexcessive stimulation)
D.) Overexcessive histaminergic responses (within the brain)
E.) Brain is saturated with glucose/glutamate

LSD (lysergic acid diethylamide) primarily interacts with 5-Hydroxytryptamine 2A. (5-HT 2A for short). It's a G-coupled protein concentrated in the orbitofrontal cortex and the visual cortex (hallucinations...). Which, paradoxically, suppresses the delusional hallucinations with a solidified, controlable visual/abstract hallucinations. In short, it takes the place of the hard-to-control typical schizophrenic hallucinations.

Phencyclidine (PCP) and ketamine are both N-methyl-d-asparate (NMDA) receptor antagonists (like dextromethorphan, DXM) - which starve the brain of glucose (by triggering an influx of Ca + ions creating an electrochemical concentration gradient) and replicating the effects of schizophrenia. Starving the brain of glucose in the frontal cortex subsequently starves the hippocampal region and stimulates the release of dopamine - creating schizophrenic like symptoms.

However, schizophrenics respond positively to NMDA receptor antagonists!? Why, one might ask?

NMDA receptor antagonism is only one method of action - these drugs also DECREASE THE EXCESSIVE FIRING RATE OF THE THALAMUS AND THE ANTERIOR CINGULATE CORTEX - i.e., not sending out as many mixed, disorganized messages. (It narrows the funnel to your conscious awareness, screening out the would-be-debilitating stream of thoughts).


With respect to other symptoms on the list, schizophrenics also respond well to antipsychotics which mainly target the decrease of dopamine, decrease of norepinephrine, increase 5-HT 2A, and act as antihistamines.

Hope the helps - I love dissociatives, the brain, and pharmacology, as well as clinical disorders.

Reputation Comments on this post:

	Many thanks! Very informative read!
	great info over a couple interesting topics. would love to read the full thing!
	Interesting and informative. And yes, it would be great to read in its entirety.

[cra$h]

Swim's never experienced a dissociative, but has experienced psychedelics, most notably lsd, and can't imagine a schizophrenic being anything like that. The closest drug to schiz swim would imagine is diphenhydramine. The symtoms are extremely realistic hallucinations, a strange sense of paranoia, aka strung out, and the whole body is just, out of whack to put into simple terms. If you really want to know what it's like being schizophrenic, pop a shitload of benadryl.

But bringing up the relationship to antihystamines got me thinking why don't doctors follow that potential lead. kind of like creating the opposite, but picking out the conscious altering parts. I don't know, that's why I'm schooling and on this site!