Cannabis: some further factsProfessor
Susan Greenfield: January 2002
Despite extensive evidence reviewed by Ameri
(1999 Progress in Neurobiology Vol 58, pp 315-348) concerning
the effects on the neurochemistry and pathology of the brain,
there is some cynicism regarding doses used experimentally, and
how one can extrapolate from what is seen as a caricature laboratory
situations to the "normal" human ones. In particular,
Chiang and Burnett (1984 Clin Pharmacol Ther Vol 36, pp
234-238) report that hippocampal neurons in vitro treated
with the same dose of THC as found in a single marijuana cigarette,
is enough to kill 50 per cent of neurons within six days. A 10-fold
higher concentration, 10µM, kills cells within three hours.
Against the argument that this is an overly
large dose, is the evidence that it is a receptor mediated effect
(Chan et al, 1998 J Neuroscience Vol 18, pp 5322-5332)
and therefore cannot be attributed to non-specific membrane damage.
Moreover, the assumption that the dose given 1µM THC, is
the same as that found in human plasma, is correct. This concentration
is assuming a relatively low average dose of the active ingredient,
THC, in a cannabis cigarette of 5-10 mgs. Concentrations of THC
can be routinely higher20 mgs, and even up to 65 per cent.
The molecular weight of THC is 314.5, therefore
1 mg in one litre would be 3.18µM, and hence in a total plasma
volume of approximately three litres, 1 mg would indeed yield
1.06µM. At a 10 times higher dose this would be approximately
10µM. The peak brain concentration is about a third of that
found in the plasma, ie would be between 1-3µM, within easy
range of the concentration used in the experimental situation.
Although the exposure to this concentration
in experiments may be longer, than that taken socially, we know
that THC does remain in the body for a long time, and therefore
such concentration would be in no way sustainable.
Even after abstaining from cannabis effects
persist. (see Solowij N, 1998 Cannabis and Cognitive Function,
Cambridge University Press and Solowij N, 1995 Life Sciences
Vol 56, pp 2119-26).
Increased risk of dependence
Abstinence symptoms following oral THC administration
to humans (Haney M et al, 1999 Psychopharmacology Vol 141
pp 385-94); and Abstinence symptoms following smoked marijuana
in humans (Haney M, et al, 1999 Psychopharmacology Vol
141, pp 395-404).
Increased risk of psychotic episode
Can occur in those with no previous psychiatric
history (Maguire P et al, 1994 Schizophrenia Research Vol
13, pp 161-7) and aggravated in those already with the illness
(Hollister L, 1998 "Cannabis" Acta Psychiatr Scand
Suppl Vol 345 pp 108-18), (Linszman D, et al, 1994 "Cannabis
abuse and the course of recent-onset schizophrenic disorders"
Arch Gen Psychiatry Vol 51, pp 273-9), and (Martinez-Arevelo
M, et al, 1994 "Cannabis consumption as a prognostic factor
in schizophrenia" Br J psychiatry Vol 161, pp 648-53).