Anyone got any answers?

There are way to many studies into the effects of Cannabis on the brain both Psychologically and Neurologically to go over everything. This should at least get you started, they've studied connections between the use of cannabis and psychosis to how it effects the reward systems of the brain on the biochemical level.

The fact is that there's so much information I just don't have the time to go over everything. Most of the effects caused by the use of cannabis can be reversed by ceasing the use of it. Most of the changes to the brain should be reversible with time. The exact reason as to why cannabis is synonymous with psychosis is still relatively unknown. On the neurological level, it can cause changes to the reward system of the brain.

This link will provide you with a more detailed description of how the chemicals contained in cannabis are distributed throughout the brain on a neurological level.
http://brain.oxfordjournals.org/cgi/reprint/awg143v1.pdf

http://www.sciencemag.org/cgi/content/summary/276/5321/1967

Mills Street Clinical Research Unit, Bentley, Perth, Western Australia, Australia.

OBJECTIVE: The aim of the paper is to review the effects of Cannabis sativa on the human brain. METHOD: A selective literature review was undertaken. RESULTS/CONCLUSIONS: Cannabis sativa causes an acute and, with regular heavy ingestion, a subacute encephalopathy. There is no evidence of irreversible cerebral damage resulting from its use, although impairment of information processing might be a long-term consequence of heavy prolonged use. The precise relationship of cannabis to the functional psychoses such as schizophrenia has yet to be clarified.


Cannabis is one of the most widely used drugs throughout the world. The psychoactive constituent of cannabis, Delta 9-tetrahydrocannabinol (Delta9-THC), produces a myriad of pharmacological effects in animals and humans. For many decades, the mechanism of action of cannabinoids, compounds which are structurally similar to Delta 9-THC, was unknown. Tremendous progress has been made recently in characterizing cannabinoid receptors both centrally and peripherally and in studying the role of second messenger systems at the cellular level. Furthermore, an endogenous ligand, anandamide, for the cannabinoid receptor has been identified. Anandamide is a fatty-acid derived compound that possesses pharmacological properties similar to Delta 9-THC. The production of complex behavioral events by cannabinoids is probably mediated by specific cannabinoid receptors and interactions with other neurochemical systems. Cannabis also has great therapeutic potential and has been used for centuries for medicinal purposes. However, cannabinoid-derived drugs on the market today lack specificity and produce many unpleasant side effects, thus limiting therapeutic usefulness. The advent of highly potent analogs and a specific antagonist may make possible the development of compounds that lack undesirable side effects. The advancements in the field of cannabinoid pharmacology should facilitate our understanding of the physiological role of endogenous cannabinoids.

Cannabis Use and Psychosis: A Longitudinal Population-based Study
J. van Os1,2, M. Bak1, M. Hanssen1, R. V. Bijl3,4, R. de Graaf3 and H. Verdoux5

1 Department of Psychiatry and Neuropsychology, European Graduate School of Neuroscience, Maastricht University, Maastricht, the Netherlands.
2 Division of Psychological Medicine, Institute of Psychiatry, London, United Kingdom.
3 The Netherlands Institute of Mental Health and Addiction, Trimbos-Instituut, Utrecht, the Netherlands.
4 Research and Documentation Centre (WODC), Ministry of Justice, The Hague, the Netherlands.
5 Department of Psychiatry, Victor Segalen Bordeaux 2 University, and Hôpital Charles Perrens, Bordeaux, France.

Cannabis use may increase the risk of psychotic disorders and result in a poor prognosis for those with an established vulnerability to psychosis. A 3-year follow-up (1997–1999) is reported of a general population of 4,045 psychosis-free persons and of 59 subjects in the Netherlands with a baseline diagnosis of psychotic disorder. Substance use was assessed at baseline, 1-year follow-up, and 3-year follow-up. Baseline cannabis use predicted the presence at follow-up of any level of psychotic symptoms (adjusted odds ratio (OR) = 2.76, 95% confidence interval (CI): 1.18, 6.47), as well as a severe level of psychotic symptoms (OR = 24.17, 95% CI: 5.44, 107.46), and clinician assessment of the need for care for psychotic symptoms (OR = 12.01, 95% CI: 2.24, 64.34). The effect of baseline cannabis use was stronger than the effect at 1-year and 3-year follow-up, and more than 50% of the psychosis diagnoses could be attributed to cannabis use. On the additive scale, the effect of cannabis use was much stronger in those with a baseline diagnosis of psychotic disorder (risk difference, 54.7%) than in those without (risk difference, 2.2%; p for interaction = 0.001). Results confirm previous suggestions that cannabis use increases the risk of both the incidence of psychosis in psychosis-free persons and a poor prognosis for those with an established vulnerability to psychotic disorder. Am J Epidemiol 2002;156:319–27.

cannabis; drug utilization; psychoses, substance-induced; psychotic disorders; schizophrenia

Abbreviations: Abbreviations: BPRS, Brief Psychiatric Rating Scale; CI, confidence interval; CIDI, Composite International Diagnostic Interview; DSM-III-R, Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised; OR, odds ratio; T1, time 1 (between baseline and 1997); T2, time 2 (between 1997 (T1) and 1999).

nature. com/npp/journal/v29/n8/full/1300496a.html

(join the space, after the point).


"The Mechanism of the Psychotic Symptoms Induced by -9-THC

The psychotropic effects of -9-THC are mediated by partial agonist effects at CB-1 receptors (CB-1R) where it has modest affinity (Ki=35-80 nmol) and low intrinsic activity (Compton et al, 1992; Gerard et al, 1991; Howlett et al, 2002; Matsuda et al, 1990). However, its hydroxy metabolite has higher affinity and potency. The primary effect of cannabinoids is the modulation of neurotransmitter release via activation of presynaptic CB-1Rs (reviewed in Belue et al, 1995; Freund et al, 2003; Pertwee, 1999a). CB-1Rs are distributed with high density in the cerebral cortex, particularly frontal regions, basal ganglia, hippocampus, anterior cingulate cortex, and cerebellum (Egertova and Elphick, 2000; Egertova et al, 1998; Elphick and Egertova, 2001; Glass et al, 1997; Herkenham et al, 1991, 1990), brain regions that are relevant to both the known effects of cannabinoids and also regions that have been implicated in the putative neural circuitry of psychosis.

The effect of CB-1R activation on increasing mesolimbic DA activity may provide one explanation for the positive psychotic symptoms induced by -9-THC (Chen et al, 1990b, 1991; French, 1997; French et al, 1997; Melis et al, 2000; Pistis et al, 2002; Tanda et al, 1997). CB-1R agonists induce cfos in the NAc (Miyamoto et al, 1996) and A10 DA neurons within the ventral tegmentum (Patel and Hillard, 2003), and these effects are blocked by DA D2 receptor antagonists (Miyamoto et al, 1996) and CB-1R antagonists (Patel and Hillard, 2003; Porcella et al, 1998).

In the hippocampus, CB-1R are located primarily on cholecystokinin containing GABAergic interneurons (Hajos et al, 2000; Katona et al, 2000, 1999a, 1999b; Tsou et al, 1999). These GABAergic interneurons are believed to orchestrate fast synchronous oscillations in the gamma range, a critical process in synchronizing pyramidal cell activity (Hajos et al, 2000; Hoffman and Lupica, 2000). Gamma oscillations are synchronized over long distances in the brain and are hypothesized to 'bind' together sensory perceptions and to play a role in cognition (reviewed in Wilson and Nicoll, 2002). Abnormalities in gamma band synchronization have been reported in schizophrenia (Spencer et al, 2003). Activation of these presynaptic CB-1Rs reduces GABA release by interneurons (Sullivan, 1999; Katona et al, 1999a), which in turn would disrupt the synchronization of pyramidal cell activity (Wilson and Nicoll, 2002; Hoffman and Lupica, 2000), thereby interfering with associative functions, disrupting normal gating mechanisms, and eventually inducing psychotic symptoms.

The effects of CB-1R activation on hippocampal LTP and LTD may explain -9-THC's amnestic effects. CB-1R activation blocks LTP of CA1 region field potentials (Nowicky et al, 1987; Collins et al, 1994, 1995; Terranova et al, 1995; Misner and Sullivan, 1999) and CB-1 receptor knockout mice have been reported to show enhanced LTP (Bohme et al, 2000).

CB-1R activation also effects acetylcholine (ACH) release in an inverted 'U' dose-response manner (Acquas et al, 2000, 2001; Gessa et al, 1998, 1997; Nava et al, 2001; Carta et al, 1998). Inhibition of acetylcholine release from cholinergic hippocampal neurons located in the septohippocampal pathway may provide another mechanism for the amnestic effects of cannabinoids.

CB-1R receptor activation stimulates mesoprefrontal DA transmission (Chen et al, 1990a; Diana et al, 1998; Jentsch et al, 1997; Pistis et al, 2001). Considering that supranormal stimulation of DA D1 receptors in the PFC has been shown to impair working memory, the negative effects of cannabinoids on working memory and other cognitive processes might be related to the activation of DA transmission in the PFC. Alternatively, cannabinoids, by inhibiting GABA release from GABAergic interneurons, may also suppress a mechanism by which DA controls PFC neuronal excitability. This might lead to nonspecific activation of the PFC, which in turn may disrupt normal signal processing and result in poor integration of transcortical inputs (Pistis et al, 2001). Cannabinoids have also been shown to influence glutamatergic synaptic transmission and plasticity in the PFC favoring LTD at the expense of LTP (Auclair et al, 2000).

Finally, animal studies have demonstrated that chronic exposure to cannabis in animals can induce behavioral sensitization to subsequent cannabinoid exposure (Cadoni et al, 2001; Rubino et al, 2001, 2003) and also to amphetamine (Gorriti et al, 1999; Lamarque et al, 2001; Miyamoto et al, 1995; Muschamp and Siviy, 2002). Sensitization has been implicated as a mechanism involved in psychosis (Laruelle, 2000; Duncan et al, 1999; Yui et al, 1999). It is tempting to speculate whether the behavioral sensitization induced by cannabinoids is a mechanism for the development of psychosis associated with chronic heavy cannabis use."



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