Elevated levels of the endogenous cannabinoid anandamide have been found in the cerebrospinal fluid of medication-naïve first episode acute schizophrenia patients, and in those in prodromal states, but the level of CSF anandamide was negatively correlated with psychotic symptoms

MDMA) are two of the most widely used recreational drugs. This symposium considered their neuropsychobiological effects, both when taken singly and in combination. In neurocognitive terms, cannabis and Ecstasy/MDMA have detrimental effects on different, although sometimes overlapping, aspects of memory and cognition. Those who take both drugs can therefore display neurocognitive deficits in several areas. In neuropsychiatric terms, each drug is again linked with various problems, especially in those who have taken them regularly. However, their acute effects are opposite in terms of oxidative stress. In laboratory animals, MDMA increases oxidative stress, whereas cannabinoids decrease it. This leads to the prediction that, in humans, cannabis may be providing some degree of protection against the neurotoxic effects of MDMA. This symposium was held at the International Congress of Biological Psychiatry, Sydney Australia on 9–13 February 2004. The symposium was entitled ‘Neuropsychiatric and psychobiological consequences of cannabis and Ecstasy/MDMA use’. These are two of the most widely used recreational drugs, with polydrug use now the norm amongst illicit drug users. This meeting covered both acute and chronic aspects of their use, when taken singly or in combination. The four oral presentations were supplemented by several related poster presentations. Nadia Solowij (2004) focused on the neuropsychiatric and psychobiological aspects of taking cannabis. During acute intoxication, cannabis can induce mild hallucinations, perceptual distortions and delusions in healthy users. Evidence was presented to suggest a causal relationship between cannabis use during adolescence, and the development of depression, anxiety and schizophrenia in vulnerable individuals. Age is also an important modulating factor, with younger adolescents being particularly vulnerable, probably due to the adverse effects of cannabis on neuronal maturation. The long-term neurobiological changes induced by cannabis may lead to an increased susceptibility to psychosis, or may interact with a pre-existing vulnerability to precipitate psychosis. Cannabis is also used extensively by people with schizophrenia, despite exacerbating many of their symptoms. The mechanisms by which cannabis increases some symptoms, while apparently alleviating others, are thought to reflect complex interactions between dopaminergic, serotonergic, glutamatinergic, GABAergic, cholinergic, opioid and endogenous cannabinoid systems (Solowij, in press). An increased density of cannabinoid receptors has been found in the anterior cingulate and prefrontal cortex of people with schizophrenia, and cannabinoid antagonists are currently being assessed as potential antipsychotic agents. Elevated levels of the endogenous cannabinoid anandamide have been found in the cerebrospinal fluid of medication-naïve first episode acute schizophrenia patients, and in those in prodromal states, but the level of CSF anandamide was negatively correlated with psychotic symptoms (Leweke et al., 2004a,b). This suggests that anandamide elevation may reflect a protective mechanism or a compensatory homeostatic adaptation to neurotransmitter imbalances associated with psychosis. These findings may lead to a greater understanding of the prevalence of cannabis use in schizophrenia and self-medication hypotheses. However, the less selective targeting by exogeneous cannabinoids, as well as the differing pharmacodynamics of acute versus chronic cannabinoid administration, may explain the apparently contradictory current theories regarding cannabinoid involvement in psychosis (Solowij, in press). Chronic cannabis use can result in elevated cannabinoid tone, generating schizophrenia-like neurotransmitter conditions in the prefrontal cortex, with desynchronized cortical and subcortical neural networks, with resultant psychotic symptomatology and cognitive deficits. Long-term users of cannabis thus show impairments of attention, memory and executive processing. The progressive deterioration of cognitive functions with increasing years of cannabis use suggests a gradual developing, and possibly enduring, alteration of brain functioning (Bolla et al., 2002; Solowij et al., 2002). Finally some ongoing (unpublished) functional imaging studies were presented. The findings provided further illumination on memory functioning in long-term cannabis Journal of Psychopharmacology 18(4) (2004) 579–000 © 2004 British Association for Psychopharmacology ISSN 0269-8811 SAGE Publications Ltd, London, Thousand Oaks, CA and New Delhi 10.1177/0269881104047286 Ecstasy/MDMA and cannabis: the complexities of their interactive neuropsychobiological effects