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Brain
Cannabis and the Brain
Despite some persistent claims to the contrary, there is
no compelling evidence that cannabis use, even long-term heavy cannabis
use, causes brain damage in humans. Block et al (2000) examined 18 heavy
users and 13 controls with MRI and found no evidence of any regional tissue
changes, contrary to older reports that certain areas were atrophied
in heavy users. In experiments approximating chronic use in mice-- up to
250mg/kg/day for 2 years-- no histopathological changes were observed (Chan
et al, 1996). For comparison, an average adult who smokes one average-potency
joint per day is recieving approximately 10-30mg. Claims for cannabis-induced
brain damage in the 70's and 80's (e.g. Heath et al., 1980), were based
on a small number of rhesus monkies and used flawed experimental designs,
and subsequent rhesus studies with larger samples and higher doses found
no histopathological changes (Scallet, 1991), even with high doses of smoked
cannabis delivered via gas masks over 2 years. Iverson (p. 1264) notes that
"[w]hile it may be possible to demonstrate neurotoxic actions after exposure
of neurons to high concentrations of cannabinoids in vitro, there is little
evidence for any significant neural damage in vivo after the administration
of pharmacologically relevant doses of these drugs." To the contrary,
one of the most interesting findings in cannabinoid research during the past
decade is that THC and other cannabinoids have potent neuroprotective properties.
References
Block et al, 2000. Effects of frequent marijuana use on brain
tissue volume and composition. Neuroreport 11(3), 491-6.
To investigate CNS
effects of frequent marijuana use, brain tissue volume and composition
were measured using magnetic resonance imaging (MRI) in 18 current,
frequent, young adult marijuana users and 13 comparable, non-using
controls. Automated image analysis techniques were used to measure
global and regional brain volumes, including, for most regions, separate
measures of gray and white matter. The marijuana users showed no evidence
of cerebral atrophy or global or regional changes in tissue volumes.
Volumes of ventricular CSF were not higher in marijuana users than controls,
but were, in fact, lower. There were no clinically significant abnormalities
in any subject's MRI. Sex differences were detected in several global
volume measures.
Heath et al, 1980. Cannabis sativa: effects
on brain function and ultrastructure in rhesus monkeys. Biological Psychiatry
15, 657-690.
Iverson, 2003. Cannabis and the brain. Brain 126, 1252-70.
The active compound
in herbal cannabis, Delta(9)-tetrahydrocannabinol, exerts all
of its known central effects through the CB(1) cannabinoid receptor.
Research on cannabinoid mechanisms has been facilitated by the availability
of selective antagonists acting at CB(1) receptors and the generation
of CB(1) receptor knockout mice. Particularly important classes of
neurons that express high levels of CB(1) receptors are GABAergic interneurons
in hippocampus, amygdala and cerebral cortex, which also contain the
neuropeptides cholecystokinin. Activation of CB(1) receptors leads
to inhibition of the release of amino acid and monoamine neurotransmitters.
The lipid derivatives anandamide and 2-arachidonylglycerol act as
endogenous ligands for CB(1) receptors (endocannabinoids). They may
act as retrograde synaptic mediators of the phenomena of depolarization-induced
suppression of inhibition or excitation in hippocampus and cerebellum.
Central effects of cannabinoids include disruption of psychomotor
behaviour, short-term memory impairment, intoxication, stimulation
of appetite, antinociceptive actions (particularly against pain
of neuropathic origin) and anti-emetic effects. Although there are
signs of mild cognitive impairment in chronic cannabis users there
is little evidence that such impairments are irreversible, or that
they are accompanied by drug-induced neuropathology. A proportion of
regular users of cannabis develop tolerance and dependence on the drug.
Some studies have linked chronic use of cannabis with an increased
risk of psychiatric illness, but there is little evidence for any causal
link. The potential medical applications of cannabis in the treatment
of painful muscle spasms and other symptoms of multiple sclerosis
are currently being tested in clinical trials. Medicines based on drugs
that enhance the function of endocannabinoids may offer novel therapeutic
approaches in the future.
Scallet, 1991. Neurotoxicology
of cannabis and THC: a review of chronic exposure studies in animals.
Phamacology Biochemistry and Behavior 4, 671-676.
Several laboratories
have reported that chronic exposure to delta-9-tetrahydrocannabinol
(THC) or marijuana extracts persistently altered the structure
and function of the rat hippocampus, a paleocortical brain region
involved with learning and memory processes in both rats and humans.
Certain choices must be made in designing experiments to evaluate
cannabis neurotoxicity, such as dose, route of administration, duration
of exposure, age at onset of exposure, species of subjects, whether
or how long to allow withdrawal, and which endpoints or biomarkers
of neurotoxicity to measure. A review of the literature suggests that
both age during exposure and duration of exposure may be critical
determinants of neurotoxicity. Cannabinoid administration for at least
three months (8-10% of a rat's lifespan) was required to produce neurotoxic
effects in peripubertal rodents, which would be comparable to about three
years exposure in rhesus monkeys and seven to ten years in humans. Studies
of monkeys after up to 12 months of daily exposure have not consistently
reported neurotoxicity, and the results of longer exposures have not yet
been studied.