Cannabis

Caro Francesco,
Sta uscendo un mio articolo su
Recent Patents on CNS Drug Discovery, 2010, Jan.
1574-8898/10 © 2010 Bentham Science Publishers Ltd.
Il titolo é “Pharmacology and Toxicology of Cannabis Derivatives and Endocannabinoid
Agonists”. L’articola considera anche aspetti terapeutici futuri per i cannabinoidi ma non nasconde i problemi.

Cerco di ricopiarti qui di sotto alcuni brani del mio articolo, tutti documentati con bibliografia accreditata: spero che servano. In ogni caso, chiedi alla tua ragazza che cosa chiede alla cannabis, senza porti in modo pregiudiziale e giudicante. Ascoltala e mostra di essere solo preoccupato per la sua salute e per la tutela della sua persona. Poi, se ti vuole stare a sentire, puoi condividere con lei qualcuna di queste evidenze.

Buon Natele e Felice Anno Nuovo

Gilberto Gerra

Acute toxycity
Learning & Memory

Learning and memory skills are severely affected by
acute cannabis use. For example acute cannabis intoxication
has been repeatedly reported to cause marked changes in
subjective mental status with negative effects on neuropsychological
performance such as learning performances
and leading to reduced attention, and reduction in working
memory [19-22].
In studies investigating acute effects among non-severe
heavy users, higher doses of tetrahydrocannabinol THC have
been found associated to with impairments in planning and
control impulse tasks, with effects persisting over 4 weeks
from drug use [23]. Compared to abstinent individuals,
cannabis users showed deficits on verbal skills, visual
recognition, delayed visual recall, and short- and long-interval
prospective memory tasks [24].
Although cannabis-associated cognitive deficit seems
reversible and related to recent cannabis exposure rather than
irreversible and related to cumulative lifetime use [25], longterm
heavy cannabis use (more than 15 years) has been
demonstrated to lead to a subtle and permanent impairment
in cognitive performance, mainly in the capacity to retain
new information [26].
At neuron-anatomical levels these cannabis effects can be
explained with the ability of cannabinoid agonists to
interfere with the expression of long term potentiation (LTP)
and long term depression (LTD), the two major molecular
mechanisms of learning and memory, in key areas such as
the prefrontal cortex, the striatum, hippocampus and the
amygdala, nucleus accumbens [27].
Electro-physiological and neurochemical data have, in
fact, clearly shown that in these brain structures activation of
cannabinoid CB1 receptors by natural as well as synthetic
agonists may lead to a marked alteration of both inhibitory
GABAergic and excitatory glutamatergic neurotransmission
which play a critical role in LTP and LTD [28].
Finally, integrated studies combining brain imaging
techniques and neuropsychological tasks evidenced that
cannabis users performed significantly worse in a ‘facename
task’, and that this deficit is associated to parahippocampal
hyperactivity and frontocortical hypo-activity [29].
In a PET study, it was also shown that heavy marijuana users
tested for a modified Stroop Task have persistent deficits in
cognitive functioning associated with hypo-activity in the
left perigenual anterior cingulate cortex and the left lateral
prefrontal cortex and hyperactivity in the hippocampus. It
was suggested that these differences in brain activity may
play a role in the development of neuropsychiatric disorders
referable to chronic cannabis use including addiction [30].
Of interest, there is evidence that while cannabinoid receptor
agonists impair memory for-mation, antagonists reverse
these deficits or even act as memory enhancers [31]. At the
neurobiological level these data are supported by findings
indicating reduction in neural plasticity following cannabinoid-
agonists treatment, and increased plasticity following
antagonist exposure [32].
Locomotor performances Central cannabinoid receptors
are densely located in the caudate putamen, in output nuclei
of the basal ganglia (i.e., globus pallidus and the substantia
nigra pars reticulate) and in the cerebellum [33]. Thought the
important role of these brain structures in motor control and
coordination, it is not surprising that cannabis use is associated
with significant locomotor skill impairment [34].
Locomotor effects of cannabinoids have been well documented
in laboratory animals and in humans [35-37]. In
addition, the significance of cannabis use in driving impairment
and motor vehicle crashes has traditionally been
established in experimental and epidemiological studies.
Surveys that established recent use of cannabis by directly
measuring THC in blood showed that THC positives,
particularly at higher doses, are about three to seven times
more likely to be responsible for their crash as compared to
drivers that had not used drugs or alcohol [38].
Impairment of cognitive functions and psychomotor
skills associated with cannabis use could last longer than a
measurable THC blood concentration, with the risk for
marijuana users to become responsible in fatal or injurious
traffic accidents, even with low blood concentrations of THC
[39]. Smoking of 17mg THC has been recently demonstrated
to result in impairment of cognitive-motor skills that could
be important for coordinated movement and driving, whereas
the lower dose of 13mg THC appears to cause less impairment
of such skills in regular users of marijuana [40],
possibly in relationship to tolerance effects. Dose-related
effects of THC in motor control impairment and deterioration
of response-reaction time tasks has been well documented
also in recreational cannabis users [41].

Chronic Toxicity of Cannabis & Cannabis Derivatives
Drug Dependence
Addiction is one of the most serious consequences of
chronic cannabis use. Epidemiological data indicate that
early initiation of cannabis consumption is a significant risk
factor for abuse progression. Moreover, regular or heavy
cannabis use was found associated with an increased risk of
using other illicit drugs, abusing or becoming dependent
upon other illicit drugs, and using a wider variety of other
illicit drugs. The risks of use, abuse/dependence, and use of a
diversity of other drugs declined with increasing age [42-44].
The findings may support a general causal model such as the
cannabis gateway hypothesis in which the cannabis exposure
has an enduring impact on hedonic processing resulting in
future enhanced risk of abusing other drugs of addiction.
Despite this phenomenon has been described, the actual
causal mechanisms underlying the gateway remain unclear
and therefore its significance is debated [42-44].
Cross-tolerance and cross-sensitization between cannabinoid
agents and opiates have been clearly demonstrated in
laboratory animal studies [45, 46]. Elective blockade of
cannabinoid receptors has been demonstrated to prevent
seeking behavior for a variety of drugs including heroin,
cocaine nicotine and alcohol [45-48].

Psychiatric Comorbidity
Recent research showed that the emotional responses to
cannabinoids are not always pleasant and delightful. Rather,
anxiety and panic may also occur after activation of CB1
receptors [49]. Diagnoses of depression, with suicidal ideation
and anhedonia, and agoraphobia were reported significantly
associated with increased likelihood of cannabis use
[50-52]. In addition epidemiological data indicates that
almost 90% of cannabis dependent adults have been found
affected by concomitant personality disorders, more than
half had a paranoid disorder and more than a third suffers
from a borderline personality disorder [53]. Evidence from
longitudinal studies in different countries showed that
regular cannabis use predicts an increased risk of a schizophrenia
diagnosis or of reporting symptoms of psychosis
[54]. These relations were found to persist after controlling
for confounding variables, such as personal characteristics
and other drug use. It is unclear whether co-morbid cannabis
use occurs to self-medicate from the negative symptoms of
psychosis [55]. However data showing that a dose dependent
relationship exists between cannabis and the development of
psychiatric disorders, may suggest that cannabis use
constitutes a causal factor in the expression of psychotic
symptoms [56]. The risk of chronic psychoses like schizophrenia
seems to be related to genetic vulnerability predisposing
a subgroup of cannabis users to a higher risk [57].
Studies focusing on children and adolescents who have
hallucinations in response to cannabis use showed that
psychotic-like reaction were associated with depressive
disorder and cannabis exposure extent [58, 59]. The complex
neuro-pharmacological mechanism underlying cannabisinduced
psychotic symptoms is unclear and controversial
data are available. On one side THC could be considered
responsible of the risk for psychotic symptoms induced by
marijuana; on the other, different cannabinoids, such as
cannabidiol, could be able to attenuate the risk of psychiatric
disorders [60].
In general, early cannabis use during adolescence seems
to be closely related to an increased risk of schizophrenialike
psychoses [61, 62], and there is now sufficient evidence
to warn young people that using cannabis could increase
their risk of developing a psychotic illness later in life [63].