The bottom line is that schizophrenia afflicts almost 1% of adults worldwide, it first presents in early adulthood, and due to its leading to cognitive impairment and social withdrawal, is overrepresented in homeless and indigent populations. Current drugs are good at reducing schizophrenia symptoms, but side effects like weight gain cause patients to stop taking them.
The excitement over this new type of drug is that it targets an entirely different system in the brain. In stead of blocking dopamine, the new drug blocks glutamate an amino acid that is also a neurotransmitter. You might remember hearing that dopamine is active in the pleasure centers of the brain, but it also is used for balance control, memory and attention. Glutamate is no less important than dopamine, and is important for personality control, learning and memory.
With glutamate's importance, why weren't there the same side effects for this drug? The answer lies in how the drug works. It targets a specific receptor for glutamate, the mGlu2/3 receptor, which accroding to the Nature press release,
is involved in a feedback loop controlling glutamate release, and therefore only works when the glutamate system is very active — bouts of high activity in this system are suspected to be one of the hallmarks of the disease.Other than this, the scientists don't know exactly how the new drug produces its antipsychotic actions. I expect this is usual with new phych meds. What of the link to angel dust? Evidently, scientists clued into glutamate as a target for schizophrenia because PCP can induce psychotic symptoms in those that are not schizophrenic. PCP was also known to interfere with the glutamate signaling system.
3 comments:
"scientists clued into glutamate as a target for schizophrenia because PCP induced schizophrenia in some users"
-wince-. ahh, run this one by your local psychiatry expert did you?
i think what you mean to say here is that PCP can induce psychotic symptoms in those that are not schizophrenic. In some cases, dose, caveats, blah, blah. In some situations the symptoms when presenting, say, to an emergency room are not differentiable from those that can be exhibited by a schizophrenic person. Once the PCP wears off, however, they are fine. Thus, it is not "schizophrenia" that is induced by PCP, just highly similar symptoms. Most importantly of course, it is temporary.
It is also true that PCP (and the related drug ketamine) can precipitate the more florid psychotic symptoms in people that are indeed schizophrenic but not currently experiencing frank psychosis.
Thank you for the needed clarification. I have updated the original text accordingly.
Now... what about marijuana and psychosis?
From Rounsaville 2007, one of the usual musings/reviews that accompanies upcoming DSM revisions..
"In addition to the everyday practical challenges to differentiating "substance-induced" from "independent" psychotic disorders, a major issue related to the etiology of psychotic disorders is whether or not psychoactive substance use can be considered a "cause" of schizophrenia, a condition that has been traditionally thought of as "independent" of substance use. Recent interest has focused on the relationship of teen and young adult cannabis use to increased risk for a subsequent diagnosis of schizophrenia. In a meta-analytic review of 7 longitudinal studies, Henquet and colleagues (14) report a 2.1 odds ratio for increased risk for schizophrenia in cannabis users. Intriguing clues for a possible genetic basis for this increased use have been reported by Caspi and colleagues (15) who documented a stronger association between cannabis use and schizophrenia for subjects with the Val-Val variant of the COMT gene. From a nosological standpoint, research of this type raises important questions about the definition of the schizophrenia syndrome itself. Are episodes of "schizophrenia" that are induced by cannabis use identical with those that are not? If not, then some type of designation of a subgroup of schizophrenia would be useful for denoting this substance-induced variant. Alternatively, if the cannabis-induced syndromes are identical to independent syndromes, this suggests the value of studying cannabis effects to identify neurobiological processes underlying schizophrenia. As noted above, aside from alcohol-induced dementia, substance-induced psychoses have traditionally been considered to be time limited and the role of drugs in causing more enduring psychoses has been that of precipitating or facilitating expression of an underlying psychotic process."
this sort of thing captures the issue for me. hard to prove direct relationships from human studies, particularly given the potential for self-medication strategies in a pre-break-yet-not-normal state. and there are definitional problems. suppose someone always was psychotic when smoking cannabis, never when not. further suppose that cannabis-induced psychosis in the general public is rare. should that person be defined as disordered?
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