LSD Flashbacks

Evidence for “hallucinogen persisting perception disorder.”

After taking a dose of mescaline in 1898, the writer Havelock Ellis reported that he experienced a heightened sensitization to “the more delicate phenomena of light and shade and color” for a prolonged period after his drug experience. John H. Halpern and Harrison Pope of the Alcohol and Drug Abuse Research Center at Harvard Medical School think that the published report of his experience may represent the first description of what came to be known as a hallucinogenic “flashback.”

In “Hallucinogen persisting perception disorder: what do we know after 50 years?” authors John Halpern and Harrison Pope, Jr. make a distinction between HPPD, as it’s known for short, and the common term, “flashback.” Writing in Drug and Alcohol Dependence, the Harvard Medical School researchers concluded that “the term ‘flashback’ has been defined in so many ways that it has become virtually useless.” A flashback typically refers to a short-lived, transient, and generally benign re-experiencing of perceptual changes that accompanied hallucinogenic drug use. Hallucinogen persisting perception disorder, on the other hand, includes this re-experiencing of visual symptoms--but also results in anxiety and distress. No anxiety, no HPPD. Without that diagnostic element, you have only your garden-variety acid flashback.

Halpern and Pope collected available reports of the phenomenon, most of which were anecdotal, and at least 20 years old. Most, but not all, involved LSD. What manner of visual alterations are we talking about? Halpern and Pope list such symptoms as “geometric hallucinations, false perceptions of movement in the peripheral visual fields, flashes of color, intensified colors, trails of images of moving objects, positive after images, halos around objects,” and objects appearing larger or smaller than they actually are.

Problems of diagnosis abound. Various conditions and substances can present symptoms that sometimes mimic the symptoms of HPPD—epilepsy, migraine, certain neurological conditions, hysteria, other drugs, schizophrenia, and some mood disorders. Also, “perceptual phenomena should be sufficiently striking to be outside the range of normal experience.” Seeing bright spots in front of your eyes when you enter a dark room doesn’t count, for example.

The authors note similarities between the anxiety caused by hallucinogen persisting perception disorder and posttraumatic stress disorder (PTSD):  “Several investigators have published theoretical articles surmising that ‘flashbacks’ reflect lasting memories from the unusually distinct and powerfully emotional experiences induced under hallucinogen intoxication.”  In the case of LSD, the classic “bad trip” qualifies in this respect. Curiously, the authors found that “individuals administered LSD in therapeutic or research settings are far less likely to develop HPPD than individuals using LSD illicitly.” Moreover, a study of 500 members of the Native American Church, who had taken peyote more than 100 times, found no evidence of HPPD in that group.

Despite the diagnostic uncertainties, and the rarity of the condition, “it seems inescapable that at least some individuals who have used LSD, in particular, experience persistent perceptual abnormalities reminiscent of acute intoxication” that cannot be better explained by other conditions, and which last for weeks or months after the last exposure to hallucinogens.

Some researchers believe that persistent flashbacks are due to “disinhibition of visual processing related to a loss of serotonin receptors on inhibitory interneurons.” Which is one way of suggesting that HPPD might represent neural damage in some cases. Others see some form of neurological “kindling” effect that ignites a replay of visual effects.  In either case, one would expect to see higher rates of HPPD in heavy users, compared to more casual users—but this does not appear to be the case.

In an interview published at NeuroSoup.com, Dr. Halpern said that people suffering from HPPD seem to be photosensitive—light acts as a trigger for the reactivation of the symptoms. Halpern proposed a theory that “there is probably something different in the visual cortex of these individuals that pre-date use of an hallucinogen…. people will describe seeing ‘floaters’ in their field of vision as a child and/or that they had visual disturbances that also predated first use of a hallucinogen. So, while there may be something about LSD and HPPD, there may also be some things that are unique to this population of users, as well.”

Halpern notes that prescribing antipsychotics for HPPD “is usually not necessary or a good choice.”  And there are no confirmatory tests for the condition. He believes that the best medicine for troubling flashbacks is “reassurance.” The symptoms typically resolve without treatment within a few months for most people who seek medical attention for flashbacks. Also, this tip: “My favorite treatment is a simple pair of sunglasses. Most people with HPPD describe symptom activation or maddeningly increased intensity of symptoms when they are in bright light… Sunglasses definitely are helpful.”

Photo Credit: http://www.derandereblickwinkel.de

A River of Rage and Redemption

An interview with writer James Brown.

“Who could blame a reader, after James Frey's discredited 'A Million Little Pieces,' for being skeptical of the pyrotechnic literature of addiction?” asks Susan Salter Reynolds in her review of James Brown's “This River” in the March 20 Los Angeles Times. Besides, it’s a cliché to assert that former addicts always know more about drug addiction than the so-called “experts.” But Los Angeles writer James Brown, a professor of creative writing at Cal State San Bernardino, is a special case. Brown has a sharp, restless mind, a hair-raising background, and has read just about everything worth reading on the subject of addiction. In “This River,” James Brown has come not to bury us in bullshit, but to praise the ineffable mysteries of the human condition. The author writes of the time when, battered and baffled, he clung to the notion of sheer will, of having total mastery over his own destiny—even as the devastating deconstruction of everyday life that drug addiction produces was proceeding apace all around him.

What saved him from dying of drug-related misadventures, like his brother and his sister and a shocking number of his childhood friends? “This River” is no ordinary tale of redemption, but rather a dogged, unadorned, very human description of one man’s attempts to understand his disorder, and to find some way to control it.

 I asked Brown if he would submit to a brief Q and A by email to be published here at Addiction Inbox, and he graciously agreed.

Q. Recent surveys suggest that kids who had their first drink at 12 or 13 are far more likely to experience alcohol dependence as adults. Did you have any early formative experiences with alcohol or other drugs that in hindsight seem significant to you?

James Brown: I’ve heard about this survey, along with another statistic cited in Under the Influence: A Guide to the Myths and Realities of Alcoholism by Milam and Ketcham that children born to an alcoholic mother or father have a four times greater chance of becoming alcoholic themselves than if they’d come from teetotaler parents. 

 Given both studies, if there’s truth to them, and I believe there is, I got off to a great start. I took my first hit of marijuana when I was nine, by twelve I’d begun drinking, and by fourteen I had my first taste of heroin. Alcohol and drugs were a way of life in the neighborhoods I grew up in, poor neighborhoods in poor apartment complexes, where nearly all of the kids were raised by single parents, typically mothers.  

All the kids I knew and hung out with drank and used. I lost contact with nearly all of my childhood friends over the years, but one became a heroin addict and bank robber (and a good one, if there is such a thing, with over 40 robberies before he got caught), and is currently in San Quentin; another shot one too many loads of meth and died of a heart attack in his 40’s; and a good friend, one of my best friends, is still hanging in there. He always loved his marijuana and now gets it prescribed, but he’s quit drinking.

So if I’m any example, and if my childhood friends are any example, I’d have to say, based on personal experience, that I believe there is a strong connection between addiction and getting off to an early start at it.

Q. Tom McGuane once referred to alcoholism as "the writer's black lung disease." Why do you think so many prominent writers have been addicted to alcohol or other drugs?

James Brown: The list of alcoholic writers is long: Hemingway, Kerouac, Eugene O’Neil, Dorothy Parker, Fitzgerald, Jean Rhys, Poe, Faulkner, and on and on. The only rationalization I can come up with, at least in regard to my own addiction, is spending long, long hours alone in a room, trapped in my own head, imagination, feelings, memories and thoughts, and when it’s time to resurface, to leave that room and return to the world that exists outside the sheltered perimeters of my mind, I’d want a drink to ease myself back into it. Without that drink, and the many that followed it, because not even from the beginning could I or did I want to stop after just one or two, it was stimuli overload.  Lights seemed brighter.  Noises louder. I was expected by my wife and children to just return to earth and join their lives when a big part of me was still locked up in that room.

But these are rationalizations. As the years passed, and the alcohol and drugs took greater hold of me, using and drinking was no longer about easing back into the world but eluding it altogether, where I didn’t have to feel or think.   Did booze or drugs help me creatively? No. That’s myth, a lie, this notion of the tragic artist. Outside of Kerouac’s On The Road, which he wrote on speed, and Stevenson’s Dr. Jekyll and Mr. Hyde, which he purportedly completed in 21 days spun on coke, and maybe a few other writers, maybe a dozen other exceptions, generally speaking writing under the influence typically produces work that reflects an insensible, messed-up consciousness.  That’s scribbling, not writing. Good writing requires clarity of mind and vision. 

Q. Can you describe your experience with the controversial drug Seroquel?

James Brown: For me Seroquel has been something of a miracle drug and helpful in maintaining my sobriety. As I’m sure you already know it’s categorized as an antipsychotic and classified as a “major tranquilizer,” as opposed to the “minor tranquilizers,” typically members of the benzodiazepine family. Why Seroquel has become a drug of abuse, I have no idea, because it doesn’t get you high, at least not for me, and there’s no sense of the euphoria associated with Valium and Xanax. Why there’s this big push (all the TV ads) to prescribe it for those suffering from depression, I also have no idea, other than the obvious, which is to make the pharmaceutical companies more money. Seroquel is potent stuff, and was prescribed to me for manic-depression (I prefer this term because it more aptly describes the nature of the illness than the euphemistic “bipolar”), post-traumatic stress syndrome and mild schizophrenia.

It took my nervous system about a week or better to adjust, with side effects of blurred vision and garbled speech, but once the sides passed the drug made a major difference in my ability to sleep without the nightmares that have plagued me for many, many years. Also, it made a big difference with the mania aspect of my mental illness, keeping my system at a relatively even keel, but I can only take it at night. If I use it during the day, I can’t function well, I can’t think clearly or quickly, and I have to be focused when I teach and write.  For depression, I use Wellbutrin, which is effective for me.  Again, I don’t understand, or agree, with the aggressive marketing of Seroquel.  It’s nothing to mess around with and should only be taken if absolutely necessary for ones mental stability.

The Ghost in the Receptor

The “spiritual” thing.

It often seems as if the proponents of the biological view are offering a take-it-or-leave-it view of human nature and behavior. The gene proposes and the neuropeptide disposes. But one important attribute of the brain’s receptor systems is that they are not static. The number and density of receptor fields, the sensitivity of individual receptors, and the “stickiness” of the cell membranes themselves all differ at different times.

We have come a long way in our understanding of “unconscious” bodily processes. Yogis demonstrated decades ago that such internal states as breathing rate, blood pressure, and the generation of certain brain waves, once thought to be impervious to volitional control, could in fact be “mentally” influenced. With the proper five-minute introduction, most people can learn to change the surface temperature of their hands by a few degrees using simple biofeedback techniques. Many spiritual growth techniques center on breathing exercises, for the same reason that diet and dietary restrictions are frequently emphasized: Such activities release different neurotransmitters in the brain, the gut, and the respiratory center, and these changes can alter consciousness. Many spiritual techniques that are physical in nature were designed to produce specific changes in brain state. We do not need to soar into the metaphysical to see the wide-ranging role of neurotransmitters. Neurotransmission via receptors is clearly an evolutionary strategy well preserved in the larger scheme of things.

Nonetheless, from A.A. to Ibogaine, alternative treatments are frequently suffused with spirituality, if not outright religiosity. All the way out there, on the edge of speculation, is the notion that a disordered reward pathway might be the impetus for the religious quest, the search for existential meaning, the artistic struggle to create. God is a neuropeptide, Candace Pert once mischievously suggested. Was Martin Luther serotonin- and dopamine-deficient? How about Joan of Arc? Or Michelangelo? Is love, or hate, any less real for having neuropharmacological substrates, microscopic chemical correlates, in the brain and body?

This all sounds funny, or blasphemous, or nonsensical—but it may be the metaphorical key to A.A.’s modest successes over the years. We know with certainty that depression and addiction are deeply linked disorders. What has begun to emerge at the edges of depression and addiction literature is that religious faith, or a spiritual belief system of some kind, can sometimes be of value in the battle against depression, drugs, and drink. This does not mean that any sort of correlation between recovery and prayer, or between decreased depression and frequency of church attendance has emerged. Nevertheless, feelings are not just feelings. Emotions influence our health, our evolutionary fitness, our learning, and our decision-making. There is the recurrent suggestion in some of the work that the additional factor at play is something researchers have referred to as “intrinsic religiosity.” People recover from all sorts of mental and physical afflictions and frequently give credit to their religious beliefs. Whatever we choose to call it, successful recovery from serious illnesses of the mind and body frequently seem to call for a fundamental shift in mental processes. Sometimes the emotional impulse that kicks off a successful recovery comes in a form identified as “spiritual.”

As Andrew Newberg and Eugene D’Aquili conclude in “Why God Won’t Go Away,” “It only means that humans have a genetically inherited talent for entering unitary states, and that many of us interpret these states as the presence of a higher spiritual power.”

Graphics Credit: http://www.theaddictionrecoverypage.com/

The “Broken Bone” Model of Addiction Treatment

A word about chronic illnesses.

It’s not always easy to conceive of addiction as a complex disease—but it’s getting easier. There are certain similarities among chronic diseases. As with diabetes, asthma, and high blood pressure, drug addiction often requires protracted and multi-faceted treatments—treatments that typically do not produce the kinds of dramatic cures and breakthroughs that are associated with recovery from other kinds of medical conditions.

As we become increasingly comfortable with the concept of addictive disease, we risk losing sight of a crucial distinction between acute medical disorders, like infections and broken bones; and chronic disorders with multiple biological, psychological, and social components, like diabetes and addiction.

William L. White of Chestnut Health Systems, and Thomas McClellan, Executive Director of the Treatment Research Institute and until recently the deputy director of the Office of National Drug Control Policy (ONDCP) in the White House, co-authored a paper for Counselor Magazine that seeks to make the distinction clear. In “Addiction as a Chronic Disorder,” the two seasoned treatment professionals point out that “chronic care has to be quite different from acute care,” and that all treatments for chronic diseases like diabetes and addiction have three things in common:

1) They reduce symptoms but cannot affect root causes. Such treatments “do not return the affected individual to normal.”

2) They require major changes in lifestyle and behavior for maximum effectiveness. For example, “even if individuals with diabetes regularly take their insulin as prescribed, this will not stop disease progression if they do not also reduce sugar and starch intake, increase exercise and reduce stress levels.”

3) Due to their complex nature, “relapses are likely to occur in all chronic illnesses. Increasingly, family members are being trained to also provide continued monitoring, “ the authors point out.

So far, so good. But chronic care treatment is not what addiction treatment in America is really about. Addiction treatment in both medical and private settings is frequently governed by acute care thinking—the “broken bone” model of treatment. For example:

--“Services are delivered ‘programmatically’ in a uniform series of encapsulated activities (screen admission, a single point-in-time assessment, treatment procedures, discharge, brief ‘aftercare’ followed by termination of the service relationship).”

--“Services transpire over a short (and historically ever-shorter) period of time, usually as a function of pre-arranged, time-limited insurance payments.”

-- “The individual/family/community is given the impression at discharge (‘graduation’) that ‘cure has occurred.’”

-- “Post-treatment relapse and re-admissions are viewed as the failure (non-compliance) of the individual rather than potential flaws in the design or execution of the treatment protocol.”

Some fifteen years ago, the acute care model began to fall under increasing scrutiny as the neurosciences took wing and insights related to chronic diseases of the body and brain began to accumulate. As White and McClellan are at pains to point out, heavy drinking and other forms of drug abuse do not inexorably become chronic disorders. "Many substance use problems are developmental and as such are often outgrown in the successful transition from adolescence into adulthood. Others occur in tandem with major life transitions (e.g., death of a loved one, divorce, job loss) and are resolved by time, natural support, brief professional intervention or peer-based intervention by others in recovery."

It’s the same with high blood pressure: A period of hypertension may or may not lead to a chronic condition, and at present it’s difficult to predict whose high blood pressure is likely to prove resistant to changes in diet, exercise, and weight.

Beyond the matter of treatment, what do chronic diseases like asthma, diabetes, and addiction really have in common?

--They are influenced by both genetic and environmental risk factors.

--They have “a prolonged course that varies from person to person in intensity and pattern.”

--They are accompanied by “risks of profound pathophysiology, disability and premature death.”

--They have effective treatments, and “similar remission rates, but no known cures.”

If substance dependence is like other chronic illnesses, then two important insights follow: 1) “Acute care models of intervention for severe substance dependence may reduce substance use temporarily but those reductions are not likely to sustain once care stops,” and 2) “methods used in the treatment of other chronic illnesses might be effectively adapted to enhance long-term recovery from substance dependence.”

In the end, the authors argue that acute forms of treatment applied to a chronic disorder “offer an explanation of the generally high and rapid rates of relapse following cessation of most available addiction treatments: there is simply no quick fix for the most severe forms of this disorder.”

Graphics Credit:  http://www.mdjunction.com

Treadmill Rehab

The curious connection between exercise and getting high.

A Vanderbilt study published in the journal PLoS ONE has confirmed what readers of Addiction Inbox have known for some time: Exercise often helps to curb cravings for addictive drugs. The Vanderbilt paper is noteworthy for focusing on heavy marijuana smokers (6 joints per day) who had not expressed any interest in quitting. Yet, at the end of a modest two-week exercise regimen, the participants reported less cannabis use.

Last August, I wrote about a growing body of research suggesting that the runner’s high and the cannabis high were more similar than previously imagined. Investigators wired up college students, put them to work in a gym, and found that “exercise of moderate intensity dramatically increased concentrations of anandamide in blood plasma.”

The British Journal of Sports Medicine ran a research review, “Endocannabinoids and exercise,” which seriously disputed the “endorphin hypothesis” assumed to be behind the runner’s high. The primary problem is that the opioid system is responsible for respiratory depression, pinpoint pupils, and other effects distinctly unhelpful to runners and other strenuous exercisers.

Compared to endorphins, the analgesia produced by the endocannabinoid system is much more consistent with the demands of exercise. Very high doses of marijuana tend to have a sedating effect, but low doses tend to induce activity or hyperactivity. There are cannabinoid receptors in muscles, skin, and the lungs. Moreover, “cannabinoids produce neither the respiratory depression, meiosis, or strong inhibition of gastrointestinal motility associated with opiates and opioids,” according to the research review. "This is because there are few CB1 receptors in the brainstem and, apparently, the large intestine.”

In addition, in my 2008 post entitled “Battling Addiction with Exercise,” I highlighted director Nora Volkow’s remarks at a NIDA-sponsored conference on addiction treatment and research. "Exercise has been shown to be beneficial in so many areas of physical and mental health," Volkow said. "This cross-disciplinary meeting is designed to get scientists thinking creatively about its potential role in substance abuse prevention."

At the same conference, Dr. Bess Marcus of Brown University, working on a NIDA-funded study of exercise for smoking cessation, presented the scientific evidence for the addiction/exercise connection. Similarities in the effects on the reward pathways of the brain's limbic system--dopamine activity in particular--may tie the two behaviors together more directly than previously thought. Among the findings:

--Rats in cages with running wheels show less interest in amphetamine infusions than rats without exercise options.

--Baby monkeys who don't roughhouse with their peers have higher levels of impulse control problems and alcohol use when they get older.

--In humans, exercise is known to reduce stress and tension--and anxiety is a well-known side effect of withdrawal, from alcohol and cigarettes to heroin and speed.

--Physical activity may enhance cellular growth in key areas of the brain involved in addiction, thereby aiding the neural changes that take place during detoxification and withdrawal from addictive drugs.

Photo Credit: http://www.livestrong.com/

NIDA on Drugs, Brain, and Behavior

How Science Has Revolutionized the Understanding of Drug Addiction.

Addiction to alcohol, nicotine, and other drugs costs Americans as much as half a trillion dollars a year, according to the National Institute on Drug Abuse. Since the 1930s, when the science of addiction got its start, scientists have consistently battled against a prevailing view of addicted individuals as morally flawed and lacking in willpower. In an effort to dispel myths and keep drug arguments on track, NIDA has released an updated 2010 version of its valuable publication, “The Science of Addiction.” The report is available as a PDF for download.

As a disease that affects both brain and behavior, addiction is indeed the “cunning, baffling and powerful” disease described by Bill W., the founder of AA. Dr. Nora Volkow, director of NIDA, said that despite the plethora of scientific advances being made in addiction medicine, “many people today do not understand why individuals become addicted to drugs or how drugs change the brain to foster compulsive drug abuse. This booklet aims to fill that knowledge gap by providing scientific information about the disease of drug addiction, including the many harmful consequences of drug abuse and the basic approaches that have been developed to prevent and treat the disease.”

Dr. Volkow exhorted Americans to “adopt science-based policies and programs that reduce drug abuse and addiction in their communities, and support scientific research that improves the Nation's well-being.”

Today, "thanks to science,” writes Volkow, “our views and our responses to drug abuse have changed dramatically. Groundbreaking discoveries about the brain have revolutionized our understanding of drug addiction, enabling us to respond effectively to the problem.”

Seeking a Patch or a Pill for Pot

Drug treatments for marijuana withdrawal.

Sometimes it’s easy to forget that marijuana is the most widely used illegal drug of all. We demonize it, yet we take it for granted. We punish citizens for its possession, but we call it a “soft” drug.

The idea of marijuana as an addictive drug--for some but by no means all users—still seems preposterous to a large number of recreational pot smokers. Yet these same people have far less trouble dealing with the existence of raging alcoholics surrounded by a majority of controlled, recreational drinkers or non-drinkers.

 For purposes of this post, we are going to stipulate that sufficient scientific evidence now exists to include marijuana in the category of addictive psychoactive drugs. Heavy, daily users of marijuana sometimes find themselves in an unexpected bind if they decide to quit cold. Perhaps as many as one or two in every ten heavy pot smokers will find themselves suffering from flu-like symptoms, loss of appetite, insomnia, vivid dreams, irritability, generalized anxiety, and other side effects that can be at least as unpleasant as quitting cold turkey after a long cigarette habit.

 Why didn’t we know this earlier? Perhaps for the same reasons that we didn’t know until the 1980s, as a general piece of knowledge, that cocaine was highly addictive. (Marijuana Anonymous didn’t start up until 1989). Doesn’t that sound absurd now, the state of our understanding of cocaine’s effects only 30 years ago? For people who suffer strong and repeatable withdrawal symptoms when they try to quit smoking weed, it is equally absurd to proclaim that what they are wrestling with does not resemble a genuine drug addiction (See the Addiction Inbox thread on marijuana withdrawal, which is now approaching 1,000 comments, and which constitutes a major database of self-reported data on marijuana withdrawal).

Having identified marijuana as classically addictive for a small slice of the user population, the focus has lately turned toward human laboratory studies, although most of the human studies thus far have been open-label trials rather than controlled double-blind studies. A group of researchers at Columbia University has been testing a variety of medications in search of a compound with demonstrated effects on marijuana abstinence and withdrawal. A study published online last year examines the effectiveness of a variety of medications on the course of marijuana craving and withdrawal in users classified as marijuana dependent. In other words, they are looking for the equivalent of a nicotine patch for marijuana.

In an article for CNS Drugs, Ryan Vandrey of Johns Hopkins University School of Medicine and Margaret Haney of the New York State Psychiatric Institute, surveyed such studies as presently exist on the subject of pharmacotherapy for cannabis dependence. There are presently no clinically validated treatments for marijuana withdrawal. And, unlike the hundreds of controlled, double blind trials of pharmaceuticals for addiction to alcohol, cigarettes, cocaine, and heroin, recent research on medications for marijuana dependence has been sparse and scattershot.

 Nonetheless, the marijuana withdrawal syndrome is now well established in the scientific literature, as well as anecdotally.  Among heavy dope smokers, the authors write, cold-turkey cessation from marijuana “produces cellular changes in the brain reward pathway (increased corticotrophin-releasing factor, decreased dopamine) that have been linked to the dysphoric effects associated with withdrawal from drugs such as alcohol, opiates, and cocaine, and are thought to contribute to relapse.”

What have they discovered so far?

One obvious starting point was dronabinol, a.k.a. Marinol, the government-approved synthetic THC often prescribed for nausea, vomiting, and appetite loss due to chemotherapy. Marinol is a direct approach to the nicotine patch strategy: A substance that stimulates cannabis receptors in a manner similar to, but by no means identical with, the high produced by natural marijuana. Perhaps a regular low dose of Marinol would keep the cannabis cravings at bay among problem users trying to quit. As it turns out, not really. Some studies showed that you could reduce a pot addict’s withdrawal symptoms somewhat in a home environment with Marinol, but the dose required to accomplish this was high enough to represent potential problems of its own.

Another obvious candidate for investigation was rimonabant, a.k.a. Accomplia—but for the opposite reason. Rimonabant, which started out life as an anti-obesity medication, blocks the cannabinoid receptor CB1, so in that sense it should function roughly like Antabuse for alcoholics. It is the “anti-weed,” but as it turned out, rimonabant’s effect on cannabis receptors didn’t do the trick, either. Rimonabant “reduced the effects of smoked cannabis in two studies,” Vandrey and Haney write, “but a reduction of subjective drug effects was not consistently observed.” Furthermore, rimonabant is under suspicion for causing “adverse psychiatric effects” and is not much in favor at present.

Next up, naltrexone—an opiod receptor antagonist, which blocks the effects of heroin and is used in alcohol and heroin detox and withdrawal. Naltrexone has been shown in some studies to “reduce the subjective effects of cannabinoids in humans,” the authors note. But no dice: “In cannabis users, pretreatment with high doses of naltrexone (50-200 mg) failed to attenuate, and in some cases enhanced, the subjective effects of dronabinol and smoked cannabis.” To make matters worse, “the effect of naltrexone can be overcome with higher doses of cannabis.”

Other possible anti-craving drugs for marijuana have not been as rigorously studied. An open-label investigation of buspirone, which works on serotonin and dopamine systems, caused a decline in self-reported cannabis use, and pot smokers showed marked decreases in craving and irritability—but, as these things often go, buspirone was not well-tolerated by the participants, with too many dropouts due to adverse side effects.

Lithium, a mood stabilizer commonly prescribed for bipolar disorder, has shown promise in several small studies. An open-label lithium trial by the National Drug and Alcohol Research Centre in New South Wales resulted in “significant reductions in symptoms of depression and anxiety and cannabis-related problems.” More studies are needed.

Fluoxetine, better known to the world as Prozac, has been anecdotally associated with reduced marijuana use in depressed alcohol-dependent patients, but has never been the subject of any large clinical studies with a population of users whose primary drug is marijuana.

And finally, there is a dark-horse candidate, a treatment drug sometimes employed to prevent relapse

 in cases of heroin addiction. Lofexidine is an alpha-2-adrenergic agonist that has been in use for years in the U.K. under the name BritLofex to treat the common symptoms of heroin withdrawal, such as cramps, chills, sweating, loss of appetite, and diarrhea. Similar but less intense withdrawal symptoms also afflict heavily addicted marijuana users. In a 2008 paper published in Psychopharmacology, “lofexidene was sedating, worsened abstinence-related anorexia, and did not robustly attenuate withdrawal, but improved sleep and decreased marijuana relapse.” Lofexidine combined with THC yielded even better results.

It appears that immediate research might be most profitably focused on lofexidine and lithium. And indeed, additional studies of the two drugs for cannabis dependency are planned by NIDA.  Also, the combination of dronabinol and lofexidine appears to be worth pursuing in future clinical investigations of anti-craving drugs for marijuana.

Vandrey, R., & Haney, M. (2009). Pharmacotherapy for Cannabis Dependence CNS Drugs, 23 (7), 543-553 DOI: 10.2165/00023210-200923070-00001

Graphics Credit: http://archives.drugabuse.gov