Cannabinoids long-term effects

Two long-term effects are theoretical considerations. One is that exposure to the cannabinoids may somehow have caused a chronic or delayed posttraumatic stress disorder. In the dosage and frequency used, this is unlikely. The postexperimental effect that was most undesirable was postural hypotension. This resulted in dizziness and faintness, from which all subjects recovered. Such a stress is Insufficient to provoke a delayed or chronic posttraumatlc stress syndrome, nor is there any evidence that any such syndrome occurred. 

In this scenario, animal models may provide a useful tool for examining the potential long-term effects of in utero exposure to cannabinoids (Fried, 2002). Indeed, due to the limited life span of rodents, it is possible to undertake longterm studies, analyzing the effects of a prenatal exposure since early developmental stages till adulthood in a limited period of time (i.e., 6—12 months). 

Antonelli, T., Tanganelli, S., Tomasini, M. C., Finetti, S., Trabace, L., Steardo, L., Sabino, V., Carratu, M. R., Cuomo, V., and Ferraro, L. (2004). Long-term effects on cortical glutamate release induced by prenatal exposure to the cannabinoid receptor agonist (7 )-(4-)-[2,3-dihydro-5-methyl-3-(4-morpholinyl-methyl)pyrrolo[l,2,3-de]-l,4-benzoxazin-6-yl]-l-naphthalenylmethanone An in vivo microdialysis study in the awake rat. Neuroscience 124, 367-375. 

Psychological The cerebellum contains the highest density of cannabinoid receptors in the brain, but little is known about the effects of cannabis on cerebellar-dependent learning. The long-term effects of can-nabinoids on the cerebellum have been assessed based on Eyeblink conditioning, an associated motor learning task that pairs a conditioned stimulus (tone) to an... 

Zhuang S, Kittler J, Grigorenko EV, Kirby MT, Sim U, Hampson RE, Childers SR, Deadwyler SA. (1998). Effects of long-term exposure to delta9-THC on expression of cannabinoid receptor (CBl) mRNA in different rat brain regions. Brain Res Mol Brain Res. 62(2) 141-49. 

Misner DL, Sullivan JM (1999) Mechanism of cannabinoid effects on long-term potentiation and depression in hippocampal CA1 neurons. J Neurosci 19 6795-6805 Moore SA, Nomikos GG, Dickason-Chesterfield AK, Schober DA, Schaus JM, Ying BP, Xu YC, Phebus L, Simmons RM, Li D, Iyengar S, Felder CC (2005) Identification of a high-affinity binding site involved in the transport of endocannabinoids. Proc Natl Acad Sci USA 102(49) 17852-7... 

Paton GS, Pertwee RG, Davies SN (1998) Correlation between cannabinoid mediated effects on paired pulse depression and induction of long term potentiation in the rat hippocampal slice. Neuropharmacology 37 1123-1130... 

Misner DL, Sullivan JM (1999) Mechanism of cannabinoid effects on long-term potentiation and depression in hippocampal CAl neurons. J Neurosci 19 6795-6805... 

Effects of cannabinoids on the sympathetic nervous system have been studied in isolated tissues and in pithed animals (Table 4). Sympathetic neurons were usually activated by electrical stimulation. Activation of CBi receptors led to inhibition of noradrenaline and/or ATP release and, consequently, to inhibition of the effector responses in the heart, in mesenteric and renal blood vessels and in the vas deferens. Figure 5A shows that cannabinoids inhibit sympathetic neuroeffector transmission in the heart. Sympathetically mediated vasoconstriction was inhibited in many tissues of pithed rats and rabbits. Sympathetic tone is depressed during long-term A -tetrahydrocannabinol administration in humans the presynaptic inhibitory effect of cannabinoids on sympathetic axon endings maybe the basis of this effect. 

In addition to their short-term effects, cannabinoids also modulate the induction of long-term synaptic plasticity. Administration of THC and the endocannabinoids anandamide and 2-AG inhibits the induction of long-term potentiation (LTP) in the hippocampus (Nowicky et al. 1987 Terranova et al. 1995 Stella et al. 1997) and long-term depression (LTD) within the cerebellum and nucleus accumbens (Levenes et al. 1998 Hoffman et al. 2003a). 

The anecdotal reports of effects of smoking cannabis on cognitive processes has naturally prompted investigation into the effects of cannabinoids on synaptic plasticity, and in particular long-term potentiation (LTP). To summarise 17 years of effort, it has been easy to show that cannabinoids have effects on LTP, and most commonly suppress it, but far more difficult to define the mechanisms by which this occurs. Emerging themes are that the commonly reported inhibition of LTP by synthetic cannabinoids may be mediated by non-CBi receptors, and that the function of the endogenous cannabinoid system may be to facilitate induction of LTP. The vast majority of studies have focussed on synaptic plasticity in the CAI region of the rat hippocampal slice and we will start our review there. 

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