Some Background on the Psychedelic Renaissance

Ecstasy, MAPS, and Post-Traumatic Stress Disorder.

The psychedelic drugs, new and old, are not only among the most powerful ever discovered, but are also tremendously difficult to study and utilize responsibly. By the mid-1990s, rumors about Ecstasy (MDMA) toxicity were everywhere. Unlike Prozac, but very much like LSD, Ecstasy not only blocks serotonin uptake, but also causes the release of additional serotonin, much the way cocaine and amphetamine cause the release of extra dopamine.

A study conducted by neurologist George Ricaurte at John Hopkins University under NIDA sponsorship seemed to show conclusive evidence of neurotoxic damage to the serotonin 5-HT receptors in the brains of monkeys given large doses of MDMA. A follow-up study of 30 MDMA users (existing users, since researchers didn’t have government permission to give MDMA to test subjects) showed 30 per cent less cerebrospinal serotonin, compared to a control group. However, the Johns Hopkins team did not have any baseline measurements for the MDMA users, and other neurologists raised technical objections about various aspects of the study, including dosage levels. As was often the case in such studies, the monkeys had been given a whopping dose, compared to the typical raver’s dose. Ricaurte insisted that the amount of MDMA consumed by a typical user in one night of raving was possibly enough to cause permanent brain damage. The government estimates that 10 million Americans have taken Ecstasy.

That would seem to be the end of the story, and a sobering lesson for today’s youth—but that is not how it turned out. A few years later, Dr. Charles Grob, psychiatry professor at the UCLA School of Medicine, received the first FDA approval ever given for the administration of MDMA to human volunteers. The result of Grob’s testing was that none of the volunteers showed any evidence of neuropsychological damage of any kind. In testimony before the U.S. Sentencing Commission, which was considering harsher penalties for MDMA possession in 2001, Dr. Grob seriously questioned the methodology of the Ricaurte studies: “It is very unfortunate that the lavishly funded NIDA-promoted position on so-called MDMA neurotoxicity has inhibited alternative research models which would better delineate the true range of effects of MDMA, including its potential application as a therapeutic medicine.” Science retracted its coverage of the Ricaurte findings.

It was eventually discovered that Dr. Ricaurte’s monkeys had been injected with amphetamine, not with MDMA—a discovery that also nullified four other published papers. Dr. Ricaurte explained that some labels had been switched, and a Johns Hopkins spokesperson called the whole thing “an honest mistake.” The basic questions about Ecstasy remain unanswered. Is there a line that separates a conceivably therapeutic dose of Ecstasy for mental ills or addictive ills from a possibly brain-damaging run of several dozen high-dosage trips? Perhaps the permanently altered receptor arrays, if they exist, don’t affect cognition or emotions in any significant way over the long run. Still, the risks of overindulgence appear to be at least potentially higher than the risks of overindulging in LSD or Ibogaine. All of the psychedelics tend to be more self-limiting than other categories of psychoactive drugs, anyway. After two or three days, even the most die-hard raver or LSD head is usually ready to take a break.

Rick Doblin and others at  the Multidisciplinary Association for Psychedelic Studies (MAPS) are now working with government investigators to pursue MDMA for the treatment of post-traumatic stress disorder. There are reports that very low doses of LSD sometimes have an antidepressant effect. One thing we know for certain is that people on SSRI medications or MAO inhibitors report that their experiences on LSD or Ecstasy are shorter and far less powerful than is typically the case.  There appears to be some competition for receptor sites when Zoloft meets LSD. In contrast to the diminished psychedelic experience while on SSRIs, the older norepinephrine-active tricyclics like Tofranil and Norpramine reportedly serve to potentiate the LSD or MDMA experience. None of these combinations is a wise idea, due to uncertainties about the interactions.

Even DMT, which experienced trippers compared to being shot out of a cannon, has returned as a legitimate study subject. Dr. Rick Strassman, then with the University of New Mexico’s School of Medicine, received approval for clinical testing of DMT. Strassman was drawn to the subject because of the molecule’s natural occurrence in the brain (which makes every man, woman, and child in America a drug criminal, chemically speaking). He gave DMT to 60 human volunteers over a study period of five years. Strassman was primarily interested in near-death experiences and mystical experiences. None of the supervised DMT sessions evidently resulted in any detectable harm to the participants. Strassman presents his views on the medical use of DMT in his book, DMT: The Spirit Molecule.

Adapted from The Chemical Carousel: What Science Tells Us About Beating Addiction by Dirk Hanson © 2008, 2009.

Graphics Credit: http://hightimes.com/

Three Drug-Related Posts (Good Ones)

And a plea for your vote.

The DrugMonkey blog, written by an anonymous NIH-funded biomedical researcher,  takes on the question of why doctors dislike narcotics abusers but tolerate drinkers and smokers, and investigates whether there is something about opiates that “turns you into a jerk" in a post titled “Does one drug cause the user to be more annoying?”

Also at DrugMonkey this month, “UK Bans Mephedrone” is  a succinct summation of the dizzy panic going on in the UK over a new party drug that has similarities to the African drug khat. Did Britain institute a hasty and ill-considered ban on the substance based on political rather than scientific concerns?

Over at the Neuroskeptic blog, a British neuroscientist presents some intelligent background to the renewed interest in psychedelic research in his post, “Serotonin, Hallucinations & Psychosis.”

And lastly--although this couldn't possibly be any more off topic--my favorite tourist village--Ely, Minnesota--is currently leading the contest for "American's Coolest Small Town" at Budget Travel magazine's online site HERE.

If you are at all familiar with Ely (Gateway to the Boundary Waters Canoe Area Wilderness, Land of Sky Blue Waters, Canoe Capital of America, Summer Home to Ten Thousand Paddling Boy Scouts) vote early and vote often! Contest closes May 9.

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

Liking It Vs. Wanting It

The Joylessness of Drug Addiction.

Hedonism, the pursuit of pleasure for its own sake, is not really the answer to the riddle of drug addiction. The pursuit of pleasure does not explain why so many addicts insist that they abuse drugs in a never-ending attempt to feel normal. With compulsive use and overuse, much of the pleasure eventually leaches out of the primary dysphoria-relieving drug experience. This does not, however, put an end to the drug-seeking behavior. Far from it. This is the point at which non-addicts tend to believe that there is no longer an excuse—the pleasure has dribbled away, the thrill is gone—but even when addicts aren’t getting the full feel-good benefits of the habit, they continue to use.

And now we know why. Any sufficiently powerful receptor-active drug is, in its way, fooling Mother Nature. This deceit means, in a sense, that all such drugs are illicit. They are not natural, however organic they may be. Yet, the human drive to use them is all-pervasive. We have no real built-in immunity to drugs that directly target specific receptors in the limbic and cortical pleasure pathways. 

The act of “liking” something is controlled by the forebrain and brain stem. If you receive a pleasant reward, your reaction is to “like” it. If, however, you are anticipating a reward, and are, in fact, engaging in behaviors motivated by that anticipation, it can be said that you “want” it. The wholly different act of wanting something strongly is a mesolimbic dopamine-serotonin phenomenon. We like to receive gifts, for example, but we want food, sex, and drugs. As Nesse and Berridge  put it, “The ‘liking’ system is activated by receiving the reward, while the ‘wanting’ system anticipates reward and motivates instrumental behaviors. When these two systems are exposed to drugs, the “wanting” system motivates persistent pursuit of drugs that no longer give pleasure, thus offering an explanation for a core paradox in addiction.” 

The absence of pleasure does not mean the end of compulsive drug use. Researchers are beginning to understand how certain drugs can be so alluring as to defeat the strongest of people and the best of intentions. It certainly does not eliminate the pain of drug hunger, of craving, to know that it is physically correlated with “a pathological overactivity of mesolimbic dopamine function,” combined, perhaps, with “increased secretion of glucocorticoids.” For such a wide variety of drugs, exhibiting a wide variety of effects, the withdrawal symptoms, while varying by degree, are nonetheless quite similar. The key, as we have seen, is that the areas of the brain that control “wanting” become sensitized by reward pathway drugs.

Under the biochemical paradigm, a runaway appetite for non-stop stimulation of the reward pathway is a prescription for disaster. The harm is physical, behavioral, and psychological—as are the symptoms. Peer pressure, disciplinary difficulties, contempt for authority—none of these conditions is necessary for drug addiction to blossom. What the drug itself does to people who are biologically vulnerable is enough. No further inducements are required. 

Graphics Credit: http://rmcute.multiply.com/

Detoxifying with Marijuana Anonymous

                            

What MA has to say.

Marijuana Anonymous was formed in 1989 as a program for those having difficulty remaining abstinent from marijuana. It is based on the 12-Step approach formulated by Alcoholics Anonymous. The group was founded in California as an amalgamation of existing groups, such as Marijuana Smokers Anonymous in southern California and Marijuana Addicts Anonymous in San Francisco. (In 1978, Pot Smokers Anonymous was founded in New York by David and Pearl Izenzon.)

But what, exactly, does Marijuana Anonymous say about marijuana? What does the organization actually suggest, in addition to the 12 Steps, when it comes to abstaining from cannabis?

The following information was excerpted from the official home page of Marijuana Anonymous and from pamphlets made available by the group.

Can there be physical effects from quitting marijuana?

In spite of numerous years of being told that there are no physiological effects from marijuana addiction, many of our recovering members have had definite withdrawal symptoms. Whether the causes are physical or psychological, the results are physical. Others have just had emotional and mental changes as they stop using their drug of choice. There is no way of telling before quitting who will be physically uncomfortable and who will not. Most members have only minor physical discomfort if any at all. This pamphlet is for those who are having trouble and wonder what's happening to them.

What are some of the more common symptoms?

By far the most common symptom of withdrawal is insomnia. This can last from a few nights of practically no sleep at all, up to a few months of occasional sleeplessness. The next most common symptom is depression (that is, if you're not euphoric), and next are nightmares and vivid dreams. Marijuana use tends to dampen the dreaming mechanism, so that when you do get clean the dreams come back with a crash. They can be vivid color, highly emotional dreams or nightmares, even waking up then coming back to the same dream. The very vivid, every-night dreams usually don't start for about a week or so.

The fourth most common symptom is anger. This can range from a slow burning rage to constant irritability to sudden bursts of anger when least expected: anger at the world, anger at loved ones, anger at oneself, anger at being an addict and having to get clean. Emotional jags are very common, with emotions bouncing back and forth between depression, anger, and euphoria. Occasionally experienced is a feeling of fear or anxiety, a loss of the sense of humor, decreased sex drive, or increased sex drive. Most all of these symptoms fade to normal emotions by three months. Loss of concentration for the first week or month is also very common and this sometimes affects the ability to learn for a very short while.

What about physical symptoms?

The most common physical symptom is headaches. For those who have them, they can last for a few weeks up to a couple of months, with the first few days being very intense. The next most common physical symptom is night sweats, sometimes to the point of having to change night clothes. They can last from a few nights to a month or so.

One third of the addicts who responded to a questionnaire on detoxing said they had eating problems for the first few days and some for up to six weeks. Their main symptoms were loss of appetite, sometimes enough to lose weight temporarily, digestion problems or cramps after eating, and nausea, occasionally enough to vomit (only for a day or two). Most of the eating problems were totally gone before the end of a month.

The next most common physical symptoms experienced were tremors or shaking and dizziness. Less frequently experienced were kidney pains, impotency, hormone changes or imbalances, low immunity or chronic fatigue, and some minor eye problems that resolved at around two months. 

For more information, contact:

 Marijuana Anonymous World Services

P.O. Box 2912

Van Nuys, CA 91404

USA

Toll Free 1-800-766-6779

office@marijuana-anonymous.org

graphic: http://www.7h1s.com/ ©2008 - Marijuana Anonymous World Services - All Rights Reserved. 

Moonshine Makes a Comeback

But it’s still illegal.

The question has always been straightforward. Distilled to its essence, if you’ll pardon the pun: Why is it legal to brew up to 300 gallons of beer, or produce your own wine, while it is illegal to make your own “hard liquor?”

After all, distillation of spirits is the logical next step. “If you are making beer,” says Max Watman, author of Chasing the White Dog, a book about moonshine, “it’s just a matter of time that you are going to be staring at the beer and going, ‘There’s whiskey inside of that.’” The newest category of illegal distillers, Watman told the Fort Worth Star-Telegram, were “foodie folks,” the same people who “drove the home brewing craze.”

The big catch is that the distilling, sale and consumption of unlicensed liquor is still a felony or Class A misdemeanor--just as it was during the Prohibition Era--carrying a sentence of one to five, and a fine of up to $10,000.  Earlier this year, investigators in two Texas counties seized stills and small amounts of moonshine in two separate raids, according to the Star-Telegram article by Steve Campbell.  Recently, a Kentucky man was arrested in possession of 100 gallons of moonshine.

And, in perhaps the ultimate sign of the times, Willie Nelson’s bus was searched and crewmembers were arrested for pot, of course—but also for the possession of untaxed alcohol in the state of North Carolina. The Star-News Online reported that  “agents entered the bus after smelling marijuana. Inside they found a quart jar, three quarters full of untaxed alcohol, or moonshine, as well as marijuana.” Matthew Rowley, author of Moonshine!, said in the article that there “aren’t any figures about it. What I know, see with my own eyes, taste with my own mouth, it really is everywhere.”

Judging by the Internet, stills and distillery supplies do seem to be ubiquitous. However, there is another, more serious class of moonshiners, consisting of criminals who produce cheap liquor for sale to illegal booze joints in larger cities. In an article in the Norfolk Virginian-Pilot, Watman said he had sampled some of the criminal booze available at a “nip joint” in Virginia, and reported that it tasted like “some sort of experimental kerosene-powered mouthwash.” In its more lethal forms, “white lightning” can lead to fatalities from lead and alcohol poisoning. (In Russia, home brew vodka has been responsible for numerous deaths.)

Home distillers would like to see hobby distilling treated as something less than a criminal enterprise, since in most if not all cases, no sales are taking place. But it may get harder and harder to avoid the “revenooers” in the future, due to the development of portable infrared spectroscopy equipment for identifying and tracking the content of alcoholic spirits emerging from illicit home stills.

An article in Chemistry Central Journal estimates that as much as 25% of all alcohol sold and consumed worldwide is unrecorded and unregulated.

Photo Credit: http://www.blog.thesietch.org/2007/03/07/diy-ethanol/

Impulsivity and Addiction

The perils of a hypersensitive dopamine system.

The brooding, antisocial loner, the one with impulse control problems, a penchant for risk-taking, and a cigarette dangling from his lip, is a recognizable archetype in popular culture. From Marlon Brando to Bruce Lee, these flawed heroes are perhaps the ones with restless brain chemicals; the ones who never felt good and never knew why (“What are you rebelling against?” “What’ve you got?”).

A recent study at Vanderbilt University, published in Nature Neuroscience, used PET scans and fMRI imaging to suggest that impulsivity and other “antisocial” traits “predicted nucleus accumbens dopamine release and reward anticipation-related activity in response to pharmacological and monetary reinforcers, respectively.”

In other words, the Vanderbilt researchers maintained that so-called “psychopathic traits” like impulsivity and risk taking are linked to addiction and gambling by means of an overly active dopamine system. PET scans of dopamine responses to a low dose of amphetamine showed that “individuals who scored high on a personality assessment that teases out traits like egocentricity, manipulating others, and risk taking had a hypersensitive dopamine response system,” according to a press release from the National Institute on Drug Abuse (NIDA), which funded the study.

Putting a different spin on the matter, NIDA director Nora Volkow said: “By linking traits that suggest impulsivity and the potential for antisocial behavior to an overreactive dopamine system, this study helps explain why aggression may be as rewarding for some people as drugs are for others.”

Lead author Joshua Buckholtz of Vanderbilt said that “the amount of dopamine released was up to four times higher in people with high levels of these traits, compared to those who scored lower on the personality profile.  Buckholtz suggested that a pattern of exaggerated dopamine responses “could develop into psychopathic personality disorder.”

Dr. Robert Cloninger, a prominent addiction researcher, has asserted in the past that children who show a high propensity for risk-taking, along with impulsivity, or “novelty-seeking,” are more likely to develop alcoholism and other addictions later in life.

And, in interviews with the late psychologist Henri Begleiter for my book on addiction science, Begleiter insisted that addicts were stuck with a package of symptoms he called behavioral dysregulation. “Disinhibition, impulsivity, trouble fitting into society—you have certain behavioral disorders in kids who later develop into alcoholics and drug addicts,” he said. The behavior itself doesn’t cause the addiction. The dysregulated behavior is a symptom of the addiction.”

“When you talk to these people, as I have,” Begleiter said, “you see that the one thing they pretty much all report is that, under the influence of the drug, they feel much more normal. It normalizes their central nervous systems. Initially, what they have is a need to experience a normal life.”

So, it wasn’t ducktails, pool halls, tattoos, casual sex, or lack of parental involvement that caused addiction to alcohol and cigarettes and pot, and maybe cocaine and speed and heroin. It wasn’t just the “bad kids.” Irrational anger, impulsive decisions, certain compulsive behaviors like gambling—these behaviors were symptoms of the same group of related disorders that included drug and alcohol addiction, and which involved specific chemicals and areas of the brain related to reward, motivation, and memory.

The trait of impulsivity is a possible marker for addiction that may help explain why it is usually impossible to persuade addicts to give up their drugs by sheer force of logic—by arguing that the drugs will eventually ruin their health or kill them. “They tell me it’ll kill me,” sang Dave Van Ronk, “but they don’t say when.”

Consider the always-instructive case of cigarette smoking. In 1964, the Surgeon General’s Report on Smoking and Health laid out the case for the long-term ill effects of nicotine quite effectively—and millions of people quit smoking. A stubborn minority did not, and many of them still have not. Are they simply being hedonistic and irresponsible? Or are the long-term negative consequences, so dramatically clear to others, simply not capable of influencing their thinking to the same degree? Biochemical abnormalities similar to those predisposing certain people to addiction may also prevent them from comprehending the long-term results of their behavior.

Buckholtz, J., Treadway, M., Cowan, R., Woodward, N., Benning, S., Li, R., Ansari, M., Baldwin, R., Schwartzman, A., Shelby, E., Smith, C., Cole, D., Kessler, R., & Zald, D. (2010). Mesolimbic dopamine reward system hypersensitivity in individuals with psychopathic traits Nature Neuroscience, 13 (4), 419-421 DOI: 10.1038/nn.2510

Graphics Credit: http://www.nature.com/neuro/journal/

No Urine Test for Addiction

Drug wars never work.

The recognition that drug wars create crime is long overdue. More than fifteen years ago, a study of the economics of street drug dealing by the Rand Corporation confirmed that most drug dealers make more money illegally than they could possibly make through any form of legitimate employment. That equation has not changed.  For minors, drug dealing is without a doubt the best-paying job available to them. 

The effort to combat drugs has poisoned our relationships with other countries. Farmers in Latin America, Southeast Asia, and Afghanistan are not the source of the drug problem. The danger of concentrating on the interdiction of foreign shipments is that it breeds the fantasy solution—a belief that the nation’s drug problem can be solved offshore, if the barriers and borders of the United States are vigorously defended.

Drug wars weaken the force of law at home. Minor drug laws are flouted with impunity, while basic civil rights are under attack in the name of national security. Drug wars ask a lot from citizens:  weakened rules of evidence, the erosion of the doctrine of probable cause, and an end to the presumption of innocence, for starters.

A different strategy would obviate the need for these enhanced powers of repression and control. Drug wars foster a form of social hypocrisy. Many of the country’s finest doctors, scientists, judges, and legislators have routinely used illegal drugs in their past. Yet their lives were not irreparably damaged, their futures thrown on the trash heap. Millions of productive citizens now in their 40s and 50s know that youthful drug use need not be permanently deleterious. They dare not speak up, of course. The people who have the most experience with these drugs have been systematically excluded from the public debate. The emerging models of addictive disease call into question almost every aspect of drug wars as they have been historically waged.

For many Americans, the use of alcohol, cocaine, or any other addictive drug is a matter of personal recreational choice. None of the strategies employed in the drug wars of the past four decades has been able to override the fact that prohibition can only be effective with the cooperation of the citizenry. Without voluntary compliance, the only recourse is federal coercion; some Orwellian nightmare of detection, control, forced detoxification, and detention.

Only a fraction of the nation’s corporations had drug-testing programs in place in 1990, but the number has climbed dramatically ever since. Inaccuracies and false positives have bedeviled drug-testing programs from the outset. Ibuprofen, available over the counter as Advil or Motrin, registers on some tests as positive for marijuana. Cold remedies such as Nyquil, Allerest, Contac, Dimetapp, and Triaminicin all contain a substance, phenylpropanolamine, which sometimes shows up as positive for amphetamine. The list of potential false positives is a long one.

Many drug testing programs do not test for alcohol, and even if such constitutionally dubious testing programs were unerringly accurate in what they do test for, there would still be valid reasons not to adopt them. Few people would insist that the presence of alcohol metabolites in the bloodstream is incontrovertible proof of incompetence on the job. But we frequently make this assumption in the case of illegal drugs, in part because the drug tests themselves are not refined enough to reliably distinguish between casual use and consistent abuse. There is no urine test for addiction. 

Adapted from The Chemical Carousel: What Science Tells Us About Beating Addiction by Dirk Hanson © 2008.