How marijuana affects the brain

Smoke 11

Misra, Rajesh. Smoke 11. [photograph] Retrieved from: http://www.publicdomainpictures.net/pictures/160000/velka/smoke-11.jpg

 

Daniel Calder

St. Petersburg Mental Health Examiner

This article will draw on Iversen & Iversen's chapter on marijuana usage from their psychopharmacology textbook. While marijuana has quite a few alkaloids, more or less all of the pharmacological affects cannabis has on the brain is due to the compound delta-9-tetrahydrocannabinol, more commonly known as THC. This substance is most highly concentrated in the resin glands in the female flower head, as opposed to male plants. This chemical is sometimes ingested in the form of hash, which involves scraping the resin-rich glands of the flower heads.

THC is an agonist for CB-1 and CB-2; receptors in the G protein-coupled class whose natural ligands are endocannabinoids, or cannabinoids naturally occurring in the brrain. CB-1 is the most common form in the brain. CB-2, on the other hand, is primarily associated with the immune system. CB-1 receptor distribution has been mapped in both human and rat brains with the help of auto radiographic studies. Thanks to positron emission tomography brain imaging technology, it will likely soon be possible to map and image CB-1 receptors in the living human brain

Studies have shown that CB-1 receptors are primarily confined to axons and nerve terminals. On the other hand, they are typically not found in neuronal cell bodies or dendrites. The highest densities o CB-1 receptors exist in the cerebral cortex, primarily the frontal regions, hypothalamus, basal ganglia, hippocampus, cerebellum and anterior cingulate cortex. Its absence from the brain stem is why THC is a safe drug, so far as the danger of lethal overdose is concerned.

THC has been found to have potent painkiller effects. This is true of animal models when it comes to acute pain, such as that caused by chemical irritants, as well as chronic pain, such as inflamed joints or limbs sensitized by nerve damage. The manipulation of the CB-1 receptor by THC is likely the cause of this, since CB-1 receptor knockout mice do not benefit from this effect of THC. THC has been found in some cases to be as potent a painkiller as morphine; indeed, THC and opiates act synergistically when administered at the same time. However, opiate and cannabinoid systems are distinct from one another.

THC appears to produce a complex combination of both sedative and stimulant effects. THC-intoxicated mice have been found to be unusually jumpy. On the other hand, the administration of especially high doses of the chemical can produce "catalepsy," which involves the animal becoming immobile for long periods of time in an unusually posture. This has been found in humans sometimes as well.

As intimated before, scientists believe with a high degree of certainty that the psychopharmacological effects of THC is due to the activation of the CB-1 receptor in the brain. The CB-1 antagonist rimonabant has been observed to block the psychological effects of THC. As Iversen & Iversen note, THC intoxication, rather than being straightforwardly "stimulant" or "depressant," is quite complicated:

"The various stages of marijuana intoxication can be classified as the "buzz" leading to the “high” and then the “stoned” states and, finally, the “comedown.” The buzz is a transient stage, which may arrive fairly quickly when smoking. It is a tingling sensation felt in the body, head, and often the arms and legs, accompanied by a feeling of dizziness or lightheadedness.

The increase in heart rate caused by the drug may also be perceived as a pounding pulse. Marijuana smokers also commonly feel a dryness of the mouth and throat and may become very thirsty. The influence of the drug on the mind is far-reaching and varied; the marijuana high is a very complex experience. The drug is a powerful euphoriant, and mental and physical excitement and stimulation usually accompany the initial stages of the “high.”

As the level of intoxication progresses from “high” to “stoned” (if the dose is sufficiently large), users report feeling relaxed, peaceful, and calm. Their senses are heightened and often distorted. They may have apparently profound thoughts, and they experience a curious change in their subjective sense of time. As in a dream, the user believes that far more time has passed than in reality has.

The distortion of the sense of time can be reproduced in animal experiments and is the exact opposite of the effect of alcohol. The disorientation of time sense may represent a key action of the drug, from which many other effects flow."

The distorted sense of time resulting from THC intoxication may be related to racing thoughts and unusual sensations. Sufficiently intoxicated users may be incapable of a normal train of thought and difficulty in conversation. Neuropsychopharmacological abnormalities associated with THC intoxication may alter the sensory inputs of the cerebral cortex. This may result in sensory modalities overlapping and resulting in synaesthesia. Visual hallucinations may result from THC intoxication at high doses.

As noted before, THC is basically a safe drug, so far as toxicity is concerned. In a long-term toxicity studied sponsored by the National Institutes of Health in the 1960s, rats were given high doses of THC daily for several months, and sometimes, several years, and no impairment of organs, reproductive function, or cancer, was observed. Its acute effects on cognition are notable, however.

On the one hand, tasks that require vigilance and attentiveness are not effected very much, if at all. However, THC clearly disrupts short-term memory. This impairment is highly dose-dependent.

So Iversen & Iversen:
"By far the most consistent and clear-cut acute effect of marijuana is to disrupt short-term memory.

For example, if test subjects are asked to repeat increasingly longer strings of random numbers, words, or other items both in the order in which they are presented and backwards, cannabis produces a dose-dependent impairment in most studies. People intoxicated with cannabis characteristically exhibit “intrusion errors”; that is, they tend to add items to the list that were not there originally.

The drug-induced deficits in these tests become even more marked if subjects are exposed to distracting stimuli during the delay interval between presentation and recall. Marijuana makes it difficult for subjects to retain information on line in working memory in order to process it in any complex manner."

Unfortunately, while basically non-toxic, THC can be dangerous in certain contexts. For example, it can sometimes result in a psychosis known as "cannabis psychosis." This is typically the result of unusually large doses of the drug, typically ingested through food or drink. Cannabis psychosis is similar in presentation to schizophrenia, and may involve hallucinations, altered perception, flat affect, paranoia, delusions of grandiosity and control and so on. Such psychosis can occur with cocaine, amphetamines, PCP, alcohol and ketamine as well.

Whether or not THC is "addictive" is quite controversial. It is not necessary, according to the modern definition of the term, for either tolerance or physical dependence to be present in order to be "substance dependent." This means that one cannot rule out the possibility of such "addiction" even though THC does not appear to be associated with either physical dependence or tolerance (although particularly heavy users may experience such tolerance).

The standards of what constitutes addiction as found in the ICD-10 and the (now obsolete) DSM-IV open the possibility that one can speak of THC dependence:
"...the diagnosis of "substance dependence" is made as the result of a carefully structured interview, and the diagnosis rests on the presence or absence of various items from a checklist of symptoms (see Table 20–5, Chapter 20). When such assessments are made on groups of regular marijuana users, a surprisingly high proportion are diagnosed as dependent—perhaps as many as 10% of regular users.

Both major classifications of mental disorders—the DSM-IV Text Revision and the ICD-10 —include a diagnosis of cannabis dependence."
Research in animal models has suggested similarities in the potential for addiction relative to other drugs:

"A behavioral withdrawal syndrome can be seen in animals that have been treated repeatedly with THC or other cannabinoid when they are challenged with the antagonist drug rimonabant. The withdrawal signs in rats include “wet dog shakes,” scratching and rubbing of the face, compulsive grooming, arched back, head shakes, spasms, and backwards walking.

Carefully controlled studies have also shown that a reliable and clinically significant withdrawal syndrome does occur in human users. The symptoms include craving for cannabis, decreased appetite, sleep difficulty, and weight loss. The syndrome may sometimes be accompanied by anger, aggression, increased irritability, restlessness and strange dreams."

In addition to a potential for addiction, some studies suggest that THC may precipitate or exacerbate long-term psychiatric problems. In one Swedish study, for example, over 50,000 conscripts in the Swedish army submitted their drug-taking habits. After 15 years, a disproportionately large number of the 246 schizophrenic patients were associated with cannabis use.

Likewise, the ris of schizophrenia was 2.4 times greater in THC users when compared with non-users. In the case of heavy users (defined as those who had taken the drug over 50 times), the risk of schizophrenia increased to 6. Other studies have likewise suggested that cannabis use may represent an independent risk factor for schizophrenia. Other studies have more or less observed the same thing.

However, it is possible that this correlation may not represent causation:
"If cannabis use were an important cause of schizophrenia, one might expect to have seen an increase in the incidence of schizophrenia as cannabis use became more common during the past 30 years, but there is no evidence that this has occurred. Indeed, an analysis of the incidence of schizophrenia and psychotic illness in Britain showed a decline during the past decade rather than an increase."