Pharmacological Action of Hashish on Brain.

2009.05.11

Effects on the Brain

3-5 minutes following cannabis smoking the smoker feels a state of euphoria and mood elevation. These are manifested as excitation, exaltation, extreme happiness, awareness and increased friendliness. Following these effects depression of the central nervous system occurs as manifested by a decrease in motor activity and alertness. Hand steadiness and body equilibrium are disturbed. In some smokers, cannabis-induced sedation is preceded by anxiety, confusion and panic. The smoker also experiences ataxia and disturbed time perception when time seemed to pass slowly. Furthermore, the discriminative ability and avoidance or escape responses are impaired. Such effects are similar to those observed following intake of alcohol.

 

Chronic intake of hashish leads to:

  1. Impairment of learning, memory disturbance and decrease in intelligence. Indeed, cannabis smokers have low intelligence and memory quotients.

  2. Stimulation of appetite in humans; however in rats, chronic treatment with cannabis depressed the food appetite.

  3. Decrease in body temperature in most mammals. The site of action seems to be the anterior hypothalamus, the third ventricle and the 4th ventricle. However, tolerance to this effect was observed. The induced hypothermia may be due to:

    1. Stimulation of 5-HT release.

    2. Decrease in PGE2 release.

    3. Increased release of endogenous opioids.

 

These biochemical changes may decrease O2 consumption (or heat gain) and increase heat loss via-induced peripheral vasodilatation.

  1. Suppression of pain feelings (analgesia). The induced analgesia is probably due to enhanced 5-HT release and release of endogenous opiates (encephalin and endorphins). Tolerance to this effect was observed.

  2. Inhibition of the vomiting centre. Indeed administration of Δ9-THC to patients receiving anticancer drugs induced a clear anathematic effect but was not superior to that of metoclopramide.

  3. Decrease in tendency to aggressiveness and violence.

  4. Decrease in REM-sleep and prolongation of stage IV sleep. Abrupt stoppage of cannabis led to an increase in REM-sleep.

 

Chronic intake of hashish leads to precipitation of various psychotic reactions that include: paranoia, delusions, fear, mania, auditory and visual hallucinations, and disorder of thought incoherence of speech, hysteria, apathy, lethargy, dizziness, amnesia, depression, disorientation, depersonalization and loss of identity. Furthermore, high resolution computerized topographical scanning of brain of chronic marijuana user’s revealed atrophy of the caudate nucleus and the frontal portion of the brain. Similarly, there are disturbances in the electrical activity in the amygdale and hippocampus together with destruction of rough endoplasmic reticulum and changes in the synapses in the brain.

 

Sites and Mechanisms of Action of Δ9-THC

The major sites of action of Δ9-THC in the brain are the thalamus, cortex and the hypothalamus. Generally, the central depressant effects of Δ9-THC are believed to be due to:

  1. Interaction of Δ9-THC with cholesterol in the cellular membranes leading to membrane perturbation that results in disordering of these membranes and increase in their fluidity resulting in alteration in ions permeability.

  2. Inhibition of some important enzymes such as: Na, K+-ATPase, Mg-ATPase and Ca-ATPase.

  3. Elevation of brain cyclic AMP via desensitization of brain phosphodiesterase or release of central PGs.

  4. Inhibition of DNA, RNA and protein synthesis in the brain.

  5. Stimulation of release of some central neurotransmitters e.g. 5-HT, dopamine and noradrenalin and inhibition of their metabolism via inhibition of their reuptake back into their respective neurons.

  6. Inhibition of ACh release and synthesis probably via inhibition of choline uptake by the cholinergic neurons.

  7. Inhibition of GABA metabolism via inhibition of its reuptake.