Eternal sunshine of the drugless mind…

What if you could wipe the memories of drugs from your mind? What if the sweet taste of relapse was no longer a fear for recovering drug users?

Wiping drug memories

Relapse back into drug use is complex. Taking into account the environmental cues that come along with using drugs. The effect of the drug is only one part. The other part being the trigger. After a while it becomes a conditioned response, making relapse an all-too-easy mechanism to fall into.

As a treatment target, relapse remains an infant, almost non-existent field. However, recently published research suggests that the memories elicited by drug cues and contexts (those environmental factors that lead to relapse) can be diminished, and hence possibly reducing or negating their impact on relapse in both animals and people addicted to drugs.

Diminishing of those drug-associated cues is brought about by pharmacologically interference. The only problem is only one of the pharmacological compounds used is suitable for human use. This means studies done in rats have yet to be mimicked in human clinical models.

However, a non-pharmacological alternative may be possible — the “memory retrieval-extinction” behavioral procedure is used to interfere with how the cues and stimuli in addicts are formed and retrieved.

What do rats and drug users have in common?

What researchers did was to manipulate the memory processes — essentially overwriting the original memory. The so called “extinction procedure” is commonly employed clinically to suppress conditioned responses to drug cues. What they describe is a memory retrieval-extinction procedure that decreases conditioned drug effects and drug seeking in rat models of relapse, and drug craving in abstinent heroin addicts.

What is common in all of this is a reemergence of extinguished responses — that is to say it is not a long-lived effect. Either re-exposure to drugs, re-exposure to the drug-associated environment, or simply the passage of time can reinstate that memory.

Rats that were taught to self-administer cocaine and heroin were used in studies where drug-cues were formed. Then this bond was tested as the animals underwent “extinction training”. Essentially, the experiment induces the drug-associated condition, extinguished, then tested (and reinstated) by injecting the drug into the rats. The test is to see if the rats revert to old behaviour and recommence self-administering their drugs.

After being assessed one month later, only the group that had received the reminder and extinction training showed a reduced tendency to resume drug-seeking behaviour following  exposure to either drug-associated cues or a reminder injection of cocaine or heroin.

In the study, authors were able to translate their work in rats to a human clinical setting, with detoxified heroin addicts. Three groups of patients were briefly exposed to a drug-relevant video or a control; then exposed to relevant drug-associated cues and stimuli (imagery and drug paraphernalia) to see if relapse would occur. Much like in the rats, the group that had the brief 10 minute delay between the heroin video and extinction showed a significant reduction in craving and blood pressure after presentation of drug-associated cues.

This study is one that successfully mimics a pharmacological effect in a behavioural setting, despite the ambiguousness of the mechanisms at play. And hopes to formulate a new route towards different kinds of treatment targets.

Originally appearing in The All Results Journals

Milton AL, & Everitt BJ (2012). Neuroscience. Wiping drug memories. Science (New York, N.Y.), 336 (6078), 167-8 PMID: 22499932

Xue YX, Luo YX, Wu P, Shi HS, Xue LF, Chen C, Zhu WL, Ding ZB, Bao YP, Shi J, Epstein DH, Shaham Y, & Lu L (2012). A memory retrieval-extinction procedure to prevent drug craving and relapse. Science (New York, N.Y.), 336 (6078), 241-5 PMID: 22499948

Ceci n’est pas la marijuana…

“You have been assigned to the condition to smoke an active marijuana cigarette that contains THC. THC is the primary psychoactive cannabinoid that gets people high.”

Does the fact that you are told you are taking a drug effect your reaction to that drug… or the drug’s effect itself? This was the simple question posed by a group of researchers publishing in Psychopharmacology. The effect of taking a drug is one thing. The effect you expect it to have is something altogether different.

“…users believing they are smoking marijuana may compensate for expected intoxication effects when engaged in deliberate decision-making by making less impulsive and risky decisions.”

34 subjects at a time were given the task to smoke a cigarette that contained marijuana or a cigarette that contained a placebo. Participants were selected based on an interesting set of criteria; native English speakers, 18 to 30 years of age, frequent marijuana use over the past month (at least once a week and at least ten times in the past 6 months), and self-reported ability to abstain from marijuana for 24 h without withdrawal.

This was a balanced placebo design experiment, examining the relative effects of expecting to receive active marijuana. These regular marijuana smokers, randomly assigned into one of four groups:

• Told they were getting THC but got a placebo

• Told they were getting THC and got THC

• Told they were getting a placebo but got THC

• Told they were getting a placebo and got a placebo

All rather deceitful and standard practice for a placebo trial.

What came next was probably the most regimented smoking session the participants had ever undertaken. Smoking sessions occurred in a 75-square-feet ventilated smoking room, with standard-issue humidified cigarettes that are rolled at both ends. And smoked according to the “standardized paced puffing procedure” — until the ash reached a mark 10 mm from the end.

Subjects and participants were then evaluated for subjective intoxication, behavioral impulsivity, and decision-making related to risky behaviours.

The laboratory test known as the Stop Signal Task is one commonly employed as a laboratory measure of inhibitory control. In essence, it uses an external stimulus to signal participants to interrupt or inhibit an already-initiated motor response. Simply put, subjects are asked to respond as fast as they can to symbols on a screen. Then an auditory tone tells the participant that they are to try and withhold their response to the current symbol on the screen. The tone occurs occasionally, in an unpredictable way, and at various latencies after the appearance of the letter on the screen. The stop signal reaction time, is an estimation of the time an individual needs to stop their usual behavior in response to the stop signal. Active THC, regardless of whether subjects were told or expected it, impaired inhibition on the Stop Signal Task.

Out of all the participants only a small proportion suspected that they were being deceived. Suspicions about the THC content were only reported by two participants (in the Told THC/Received Placebo condition) and by seven participants (in the Told Placebo/Received THC condition). In all cases, Both THC dose and marijuana expectancy independently increased subjective intoxication.

It is commonly known that real or perceived expectancies can play a part in influencing responses to other drugs, such as alcohol. Here, expectancy of smoking THC in combination with active THC increased perceptions of risk from risky alcohol use.

The effect of THC somewhat contributed to impaired inhibition — that is the pharmacological effect and not the perceived effect. Whereas expectancy of having smoked THC affected impulsive decision-making, with a compensatory direction of effect on some measures of risky decision-making. For example, independently from the THC administration, expectancy also increased perceived risk from coercive sex among women.

Researchers showed that THC can affect some mechanisms underlying impulsive behaviors while not affecting others. The study represents the first evaluation of independent and combined effects of smoking and expecting to smoke active marijuana on multiple measures of risk taking and impulsivity, using a balanced placebo design. It proved a way to independently tease out the expectancy that marijuana was smoked from the pharmacologic effect of delta-9-tetrahydrocannabinol (THC).

Originally appearing at All Results Journals

Image — source

Metrik J, Kahler CW, Reynolds B, McGeary JE, Monti PM, Haney M, de Wit H, & Rohsenow DJ (2012). Balanced placebo design with marijuana: Pharmacological and expectancy effects on impulsivity and risk taking. Psychopharmacology PMID: 22588253

Addicted to Love…

The ultimate reductio ad absurdum argument is that any behaviour can become potentially addictive.

Which leads to the next logical question: are there any good addictions? Researchers today talk of addiction as a disease. And in that trope, the “disease concept” of addiction is really just a metaphor. A metaphor with connotations.

Researchers posit that for a behaviour to become harmfully addictive, it would involve some type of “rush” effect, time-intensive repetition, intense behavioural or cognitive preoccupation, loss of control, and negative consequences.

At this point in time, we have a long list of things that can be counted as addictive, including prayer, meditation, and even religion. But for now we focus on perhaps the oldest of all behaviours — love.

The relationship between passionate love and addiction has been debated exhaustively amongst social science circles for many years. It began with Sigmund Freud, who had intimated the existence of a similarity between amorous passion and drug addiction. Currently this is ill-defined. That is to say, there are no recognized or standard definitions or diagnostic criteria for “love addiction”, “love passion”, or “sex addiction”.

Is there a difference between love and addiction? Is being addicted to love a disease? Is social attachment an addictive behaviour?

All loaded questions with no easy answers. Some sort of parlance on the subject comes from the world experts in all things pertaining to love and sex — the French. A group of French researchers, publishing in The American Journal of Drug and Alcohol Abuse, describe the clinical distinctions between “love passion,” “love addiction,” and “sex addiction”. Using advances in neurobiology to compare clinical, neuropsychological, neurobiological, and neuroimaging data on love and passion.

They begin with the most pertinent question: “Is there any legitimate reason to associate a pathological condition (addiction) and a natural, pleasurable one [love]?”

With there being no recognized definition or diagnostic criteria for “love addiction” it is hard to posit an idea. But the bare bones of it all has some similarities to substance dependence:

“euphoria and unrestrained desire in the presence of the love object or associated stimuli (drug intoxication); negative mood, anhedonia, and sleep disturbance when separated from the love object (drug withdrawal); focussed attention on and intrusive thoughts about the love object; and maladaptive or problematic patterns of behavior (love relation) leading to clinically significant impairment or distress, with pursuit despite knowledge of adverse consequences.”

The notion of love as an addiction is described pertaining to all the usual disease addiction tropes — from a clinical description, comparing the absence of love to substance withdrawal, and — most importantly — the shift that occurs from normal to addictive state. A shift that is barely perceivable due to the simple fact that such a dependence is present in both states.

“Addiction would be defined as the stage where desire becomes a compulsive need, when suffering replaces pleasure, when one persists in the relationship despite knowledge of adverse consequences (including humiliation and shame).”

The fact that there is currently no data on the epidemiology, genetics, co-morbidity, or treatment of love addiction lead the researchers to conclude that to place some cases of “love passion” within a clinical disorder spectrum or to firmly classify it as a behavioural addiction (or to a lesser extent a disorder of impulse control) would be premature.

Addictions, particularly those to substance, short-circuit and often circumvent the natural and complex mechanisms for managing a whole range of humanistic behaviours — sensations, emotions, cognition and relationships. Add to this the fact that certain mechanisms are not well understood. Making it hard to apply it to love.

A further complication is the simple and often overlooked fact that “love” is the source of the strongest sensations, emotions, and passions known to human beings.

Originally appearing at The All Results Journal

Reynaud, M., Karila, L., Blecha, L., & Benyamina, A. (2010). Is Love Passion an Addictive Disorder? The American Journal of Drug and Alcohol Abuse, 36 (5), 261-267 DOI: 10.3109/00952990.2010.495183