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Cannabinoids 2009;4(4):1-3
© International Association for Cannabis as Medicine
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Article of the Month
THC can improve symptoms of schizophrenia
Franjo Grotenhermen
nova-Institut, Chemiepark Knapsack, Industriestraße, D-50354 Hürth, Germany
Abstract
Scientists at the Rockland Psychiatric Center in Orangeburg, New York, reported of an improve-
ment of schizophrenia symptoms in 4 patients who received oral dronabinol (THC) (Schwarcz et
al. J Clin Psychopharmacol 2009;29(3):255-8 ). Only patients with a previous history of self-
reported benefits from cannabis use were selected. In addition, they presented with a severe, re-
fractory condition that made the possible benefits outweigh the risks. Dronabinol administration
was initiated at 2.5 mg twice a day and subsequently raised to 5 mg twice a day in the second
week and 10 mg twice a day in the third week. One of the patients needed 8 weeks to reach sig-
nificant improvement, while the others responded to the therapy within a shorter period of time.
Researchers noted that "this improvement seems to have been a reduction of core psychotic symp-
toms in 3 of the 4 responders and not just non-specific calming."
Keywords: cannabis, THC, dronabinol, schizophrenia, psychosis, case report
This article can be downloaded, printed and distributed freely for any non-commercial purposes, provided the original work is prop-
erly cited (see copyright info below). Available online at
www.cannabis-med.org
Author's address: Franjo Grotenhermen,
[email protected]
Summary of Original Article
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A number of patients suffering from schizophrenia
have reported that they profit from a self-medication
with cannabis [4], but this claim has never been inves-
tigated in a clinical study. To date, epidemiological
studies reported only of a deterioration or unchanged
severity of symptoms in patients with schizophrenia by
the use of cannabis [7]. In addition, longitudinal studies
have shown, that the use of cannabis increased the risk
for the development of schizophrenic psychosis [1].
However, the risk was only increased for adolescents
and young adults and only a small proportion of users
developed a psychosis. It was suggested that vulnerable
or genetically predisposed people may experience these
negative effects from cannabis use [3].
Previously, positive consequences of cannabis use in
schizophrenic patients observed in studies were re-
stricted to its effects on cognitive performance. In two
studies, patients suffering from schizophrenia who used
cannabis showed a better cognitive performance than
patients with schizophrenia, who did not use the drug
[2,5]. However, another study found a deterioration of
neurocognitive function associated with cannabis use
by schizophrenic patients [9].
Dronabinol is the INN (international non-proprietary
name) of a natural cannabinoid, the (-)-trans-isomer of
delta-9-tetrahydrocannabinol, which is present in the
cannabis plant. It is often called THC or delta-9-THC,
since the other three isomers do not exist naturally.
Dronabinol may be extracted from the plant but also be
manufactured synthetically or semi-synthetically by
isomerization of cannabidiol [11].
It is supposed that schizophrenia could be caused by a
hyperactivity of the endocannabinoid system in at least
some patients, the so-called endocannabinoid hypothe-
sis of schizophrenia [8]. According to this hypothesis
stimulation of the endocannabinoid system would
cause psychotic symptoms, while the blockade of this
system could treat schizophrenia. The current study
shows, that in single patients stimulation of CB1 recep-
tors may result in an improvement of psychosis. It is
remarkable that the improvements were observed in
patients with severe disease, who did not respond to
other medications. It can be supposed that the high
response rate observed is based on the selection of
patients. Authors noted that the non-response to stan-
dard medication with dopamine-blocking substances
might indicate that the psychotic symptoms of these
patients were caused by changes in other systems such
as the endocannabinoid system.
Another natural cannabinoid has been shown to possess
therapeutic potential in schizophrenia. For example,
cannabidiol (CBD) was effective in the treatment of
psychotic symptoms of six patients suffering from
Parkinson's disease [12]. In another study with 42 pa-
tients with acute schizophrenia, of whom half received
800 mg CBD daily for four weeks, the cannabinoid
was as effective as amisulpride, an established anti-
psychotic drug [6]. Since CBD has a different mode of
action than THC, these two cannabinoids may be bene-
ficial in different patients.
Comment
It is well-known that dronabinol and other CB1 recep-
tor agonists may cause opposite physical effects in
different people, that they usually reduce but some-
times increase pain, that they usually reduce but rarely
cause nausea and vomiting. This may also be true for
psychiatric diseases and symptoms such as depression,
anxiety and also schizophrenia, depending on cannabi-
noid dose and individual factors such as "endocannabi-
noid tone" that are currently not well understood. We
are reminded of the complexity of the human brain and
the remaining challenge to understand its function.
References
1. Arseneault L, Cannon M, Poulton R, Murray R,
Caspi A, Moffitt TE. Cannabis use in adolescence
and risk for adult psychosis: longitudinal pro-
spective study. BMJ 2002;325(7374):1212-3.
2. Coulston CM, Perdices M, Tennant CC. The
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2007;96(1-3):169-84.
3. Degenhardt L, Hall W. Is cannabis use a contri-
butory cause of psychosis? Can J Psychiatry
2006;51(9):556-65.
4. Gieringer D. Medical Use of Cannabis: Experi-
ence in California. In: Grotenhermen F, Russo E,
eds. Cannabis and cannabinoids. Pharmacology,
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5. Jockers-Scherübl MC, Wolf T, Radzei N,
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Schreiber D, Hänsel A, Neatby MA, Juelicher A,
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March 2010, Vol. 11, No. 2_2 , Pages 208-219
Patrik Roser1, Franz X. Vollenweider2, Wolfram Kawohl, MD1*
1Research Group Clinical and Experimental Psychopathology, Department of General and Social Psychiatry ZH West, Psychiatric University Hospital Zurich, Zurich, Switzerland
2Research Group Neuropsychopharmacology and Brain Imaging & Heffter Research Center, Clinic for Affective Disorders and General Psychiatry ZH East, Psychiatric University Hospital Zurich, Zurich, Switzerland
*Correspondence: Wolfram Kawohl, MD, Psychiatric University Hospital, Militärstrasse 8, Postfach 1930, 8021, Zurich, Switzerland +41 44 296 7461 +41 44 296 7449
[email protected]
Δ9-Tetrahydrocannabinol (Δ9-THC), the principal psychoactive constituent of the Cannabis sativa plant, and other agonists at the central cannabinoid (CB1) receptor may induce characteristic psychomotor effects, psychotic reactions and cognitive impairment resembling schizophrenia. These effects of Δ9-THC can be reduced in animal and human models of psychopathology by two exogenous cannabinoids, cannabidiol (CBD) and SR141716. CBD is the second most abundant constituent of Cannabis sativa that has weak partial antagonistic properties at the CB1 receptor. CBD inhibits the reuptake and hydrolysis of anandamide, the most important endogenous CB1 receptor agonist, and exhibits neuroprotective antioxidant activity. SR141716 is a potent and selective CB1 receptor antagonist. Since both CBD and SR141716 can reverse many of the biochemical, physiological and behavioural effects of CB1 receptor agonists, it has been proposed that both CBD and SR141716 have antipsychotic properties. Various experimental studies in animals, healthy human volunteers, and schizophrenic patients support this notion. Moreover, recent studies suggest that cannabinoids such as CBD and SR141716 have a pharmacological profile similar to that of atypical antipsychotic drugs. In this review, both preclinical and clinical studies investigating the potential antipsychotic effects of both CBD and SR141716 are presented together with the possible underlying mechanisms of action.
May 17, 2007 - Berlin, Germany
Berlin, Germany: Cannabis use is associated with improved cognition in schizophrenic patients, according to clinical trial data to be published in the journal Progress in Neuro-Psychopharmacology & Biological Psychiatry.
Investigators at the University of Berlin assessed the impact of cannabis on cognitive functions in schizophrenic patients who reported prior use of pot versus patients who reported no history of substance abuse. Researchers reported that cannabis use was not associated with any decline in cognition, and that those subjects who reported using marijuana prior to their first psychotic episode showed improved cognitive performance on certain tests compared to non-users.
"[T]o our surprise, cannabis abusing schizophrenic patients … achieved results either similar to those [achieved] by the non-using cannabis schizophrenic patients or, at times, performed even better than them," investigators concluded. "[R]ather than deteriorating neuropsychological performance, cannabis [use] prior to [a patient’s] first psychotic episode improved cognition in some tests."
According to the study’s authors, cognitive dysfunctions are present in more than 80 percent of patients diagnosed with schizophrenia.
A separate 2005 study by investigators at Manchester Metropolitan University in Britain previously reported that schizophrenic patients who consumed cannabis prior to disease onset possessed greater cognitive skills after ten years than did non-users.
Neurocognitive studies performed on healthy volunteers generally report that the use of marijuana, even long-term, is not associated with any significant or long-lasting declines in cognitive function.
For more information, please contact Paul Armentano, NORML Senior Policy Analyst, at:
[email protected]. Full text of the study, "Cannabis induces different cognitive changes in schizophrenic patients and in healthy controls," will appear in a forthcoming issue of Progress in Neuro-Psychopharmacology & Biological Psychiatry.
![:\](https://bluelight.org/xf/BL_Images/Orig_Emoji/wrygrin.gif "wry grin :\")
