Cannabinoids

Human Studies of Cannabinoids and Medicinal Cannabis 741

Do any of these acute deficits persist after cannabis has been discontinued and
fully metabolised? A large and expanding scientific literature has still not fully
resolved this question. Recognising the methodological shortcomings that have
dogged much of this research, Gonzalez et al. (2002) proposed seven “minimal
criteria” which should be applied to any study purporting to explore non-acute
cognitive effects of cannabis: only 13 out of 40 eligible studies met these basic
criteria. The authors point out that negative results have been disseminated in the
media without any acknowledgement of these serious shortcomings.
A major problem lies in distinguishing long-lasting but reversible residual ef-
fects (due to slow metabolism of cannabis components or withdrawal phenomena)
from irreversible effects. Pope et al. (2002) tested 77 current heavy users and 87
controls. The former showed significant memory deficits at 0, 1 and 7 days of
abstinence, but by day 28 were virtually indistinguishable from control subjects.
There was no association between duration of cannabis use and cognitive perfor-
mance after 28 days of abstinence. This conflicts with the finding of Solowij et al.
(2002) that deficits on several neuropsychological measures were correlated with
lifetime duration of cannabis exposure. In seeking to explain this, Pope et al. (2002)
point out that even well-controlled studies depend on the assumption that, after
adjustment for more obvious confounding factors, cannabis users and non-users
are comparable on all factors other than exposure to cannabis. Additionally, heavy
use of an illegal drug may produce non-pharmacological deficits such as family
alienation or school drop-out that impact outcome measures. Grant et al. (2003)
carried out a meta-analysis of studies examining non-acute cognitive effects, and
found no substantial, systematic or detrimental effect of recreational cannabis on
neuropsychological performance. They concluded:

The small magnitude of effect sizes from observations of chronic users of

cannabis suggests that cannabis compounds, if found to have therapeutic

value, should have a good margin of safety from a neurocognitive standpoint

under the more limited conditions of exposure that would likely obtain in

a medical setting.

3.2

Dependency/Abuse

Properties of THC that may have a bearing on its dependency and abuse potential
have been investigated in numerous animal models, but how reliable these may
be in predicting human behaviour is open to question. Despite the cripplingly
expensive War on Drugs, recreational cannabis is still easily available, cheaper
in real terms and used extensively throughout the world, so it seems sensible to
examine what actually happens outside the laboratory.
The evidence for cannabis dependence in humans has been reviewed by Johns
(2001). Characteristic components of a dependence syndrome are the need over
time to take more of the drug to maintain the desired effect (tolerance), a pre-
dictable group of symptoms and signs over a consistent time course when the drug