For Some Users, Cannabis Can Be Fiercely Addictive.

For a minority of marijuana users, commonly estimated at 10 per cent, the use of pot can become uncontrollable, as with any other addictive drug. Addiction to marijuana is frequently submerged in the welter of polyaddictions common to active addicts. The withdrawal rigors of, say, alcohol or heroin tend to drown out the subtler, more psychological manifestations of cannabis withdrawal.

What has emerged in the past ten years is a profile of marijuana withdrawal, where none existed before. The syndrome is marked by irritability, restlessness, generalized anxiety, hostility, depression, difficulty sleeping, excessive sweating, loose stools, loss of appetite, and a general “blah” feeling. Many patients complain of feeling like they have a low-grade flu, and they describe a psychological state of existential uncertainty—“inner unrest,” as one researcher calls it.

The most common marijuana withdrawal symptom is low-grade anxiety. Anxiety of this sort has a firm biochemical substrate, produced by withdrawal, craving, and detoxification from almost all drugs of abuse. It is not the kind of anxiety that can be deflected by forcibly thinking “happy thoughts,” or staying busy all the time.

A peptide known as corticotrophin-releasing factor (CRF) is linked to this kind of anxiety. Neurologists at the Scripps Research Institute in La Jolla, California, noting that anxiety is the universal keynote symptom of drug and alcohol withdrawal, started looking at the release of CRF in the amygdala. After documenting elevated CRF levels in rat brains during alcohol, heroin, and cocaine withdrawal, the researchers injected synthetic THC into 50 rats once a day for two weeks. (For better or worse, this is how many of the animal models simulate heavy, long-term pot use in humans). Then they gave the rats a THC agonist that bound to the THC receptors without activating them. The result: The rats exhibited withdrawal symptoms such as compulsive grooming and teeth chattering—the kinds of stress behaviors rats engage in when they are kicking the habit. In the end, when the scientists measured CRF levels in the amygdalas of the animals, they found three times as much CRF, compared to animal control groups.

While subtler and more drawn out, the process of kicking marijuana can now be demonstrated as a neurochemical fact. It appears that marijuana increases dopamine and serotonin levels through the intermediary activation of opiate and GABA receptors. Drugs like naloxone, which block heroin, might have a role to play in marijuana detoxification.

As Dr. DeChiara of the Italian research team suggested in Science, “this overlap in the effects of THC and opiates on the reward pathway may provide a biological basis for the controversial ‘gateway hypothesis,’ in which smoking marijuana is thought to cause some people to abuse harder drugs.” America's second favorite drug, De Chiara suggests, may prime the brain to seek substances like heroin. In rebuttal, marijuana experts Lester Grinspoon and James Bakalar of Harvard Medical school have protested this resumed interest in the gateway theory, pointing out that if substances that boost dopamine in the reward pathways are gateways to heroin use, than we had better add chocolate, sex, and alcohol to the list.

In the end, what surprised many observers was simply that the idea of treatment for marijuana dependence seemed to appeal to such a large number of people. The Addiction Research Foundation in Toronto has reported that even brief interventions, in the form of support group sessions, can be useful for addicted pot smokers.

In 2005, an article in the American Journal of Psychiatry concluded that, for patients recently out of rehab, “Postdischarge cannabis use substantially and significantly increased the hazard of first use of any substance and strongly reduced the likelihood of stable remission from use of any substance.”
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source: Addiction Inbox