11/16/15

A Blood Test for Addiction?

© Judith Flacke | 123rf.com

© Judith Flacke | 123rf.com

A research team with the Scripps Research Institute has published the results of a study that shows how a specific protein molecule controls the mu-opioid receptor (MOR) in a small group of brain cells. The mu-opioid receptor is the main one activated by morphine. When study animals lacking a specific protein called RGS7 were given morphine, they had an increased reward response, increased pain relief, delayed tolerance and a heightened withdrawal response. “In other words, without the protein, the animals were predisposed to morphine addiction.”

Several news outlets, including The Fix and HCP Live described the research and its implications. The research team hypothesized that RGS7 may regulate morphine behavior through neurons located in the nucleus accumbens, part of the neural circuitry that seems to be involved in the development of addiction. Kirll Martemyanov, who led the research team, said: “The mu opioid receptor acts as a conductor of the drug’s effects, while RGS7 acts as a brake on the signal.” Laurie Sutton, one of the researchers and the lead author of the published study, said that RGS7 could be a potential target for future drug development. “Pharmacological intervention at the level of RGS7 may reduce some of the detrimental side-effects associated with opiates.”

Martemyanov also sees where their research findings have a potential future in diagnosis. There are also some implications for why certain individuals have a difficult time with opioid addiction, while others are not so susceptible. In addition to drug craving, the animals lacking RGS7 also worked harder for a food reward, suggesting RGS7 may be a more general regulator of reward behavior beyond just drug-induced euphoria.

If our findings hold true for human patients, you could look specifically for RGS7 levels for any disabling mutation with a simple blood test. . . . Mutations could indicate a strong reaction to a drug such as morphine—people carrying a deficient copy of the RGS7 gene might need much lower doses of opioids and could be cautioned to be extra careful with these substances.

Martemyanov is currently a tenured Associate Professor for the Department of Neuroscience for the Scripps Research Institute in Jupiter Florida. He has done extensive past research into the potential role of the RGS protein. Here are links to abstract for two of his previous research studies: “A Role of RGS Proteins in Drug Addiction” and “The R7 RGS Protein Family.” Here is a link to the study discussed here: “Regulator of G-Protein Signaling 7.”

Keri Blakinger for The Fix is getting a bit ahead of the research in saying it could mean a near-future genetic test for opiate addiction. Martemyanov clearly said that IF their findings held true for humans (the study was done on animals) a simple blood test for people with a deficient RGS7 gene could be done. As explained above, this would indicate a predisposition to opiate addiction because of the dysregulation that occurs with the mu receptor. A defective RGS7 gene would reinforce the euphoria and pain relief experienced with opiates, while heightening the withdrawal when the levels drop. Chasing the high or pain relief of opiates coupled with a desire to avoid the pain and discomfort of withdrawal is the classic dynamic in opiate addiction.

If the research holds true for humans, individuals with a deficient RGS7 gene could be treated with lower doses of opioids and cautioned to be careful with opioids of all kinds. Drug development that targets RGS7 would need to explore how other mechanisms are effected by the RGS7 gene. Remember that it may be a more general regulator of reward behavior beyond drug-induced euphoria. “Fixing” the addiction problem may cause another neurochemical one. Another important research question I see is whether or not the abuse of opiates leads to a dysregulation of the mu receptor similar to what Martemyanov found with a defective RGS7 gene.

Let’s see where this research takes us. It is exciting, basic research. But don’t run ahead of it, trying to anticipate where it will lead.

02/13/15

Entering Into Temptation

© : Ying Feng Johansson 123rf.com

© : Ying Feng Johansson 123rf.com

Whilst it knocks at the door we are at liberty; but when any temptation comes in and parleys with the heart, reasons with the mind, entices and allures the affections, be it a long or a short time, do it thus insensibly and imperceptibly, or do the soul take notice of it, we “enter into temptation.” (John Owen)

John Owen published Temptation in 1658 to address the nature of temptation, what it means to enter into temptation, and how to prevent it.  A previous article: “Lead Us Through Temptation,” looked at the nature of temptation. Here we begin to look at what it means to enter into temptation. Owen built each of these three facets of his work around the caution given by Jesus to his disciples in the Garden of Gethsemane: “Watch and pray that you may not enter into temptation” (Matthew 26:41).

Entering into temptation is not simply being tempted, according to Owen. We cannot expect to avoid temptation. “Whilst Satan continues in his power and malice, whilst the world and lust are in being, we shall be tempted.”  However, the Lord’s Prayer pleads that we be not led into temptation. So then it is possible that we could be tempted, but not actually enter into temptation.

Then it must be something more than the ordinary, daily business of being tempted by our lusts. Perhaps it is something to do with the seduction or allurement of sin. Entering into temptation is analogous to a man falling into a pit from which he does not see how he can escape. But the Lord knows how to rescue the godly from temptation (2 Peter 2:9).

When we entertain a temptation, we enter into temptation. But entering into temptation is not the same as being conquered by it. A person may enter into temptation, yet not fall under temptation. God can make a way for the individual to escape. She can break through the snare, and be more than a conqueror—even though she entered into temptation. Remember that Christ himself entered into temptation, but was not stymied by it.

When we enter into temptation, there is usually some special action or occasion by which Satan tempts us. Something beyond his ordinary allurements and seductions. It provokes some greater tumult, a more profound corruption than normal. Our hearts become so entangled with this desire, that we debate whether or not to act on it. And therefore we are not “wholly able to eject or cast out the poison and leaven that hath been injected.”

The entanglement continues, usually to be manifested in one of two ways. First, for reasons known only to himself, God permits Satan to have some particular advantage over the person. Second, the individual’s own lusts and corruptions encounter objects and occasions that are especially provoking. The conditions and circumstances of the person’s life appear to have been almost orchestrated to manifest the opportunity for temptation.

This state of affairs is properly called the “hour of temptation.” It is the time or season in which everything comes to a head—when we have truly entered into temptation. “Every great and pressing temptation hath its hour, a season wherein it grows to a head, wherein it is most vigorous, active, operative, and prevalent.” It may take a long time to rise up. But there is a time when, from the confluence of outward and inward circumstances, it manifests itself fully and completely.

That very temptation, which at one time had little or no power and was easily resisted, now bears the person away quite like a rushing torrent. Either it has gained new strength from other circumstances, or the person has been weakened somehow. David likely had prior temptations to adultery and murder, like in the case of Nabal; but his hour of temptation had not come. So stay alert for the hour, for who is not tempted?

There will be a time when the cravings of temptation will be more urgent; their justifications more plausible; their facades more glorious; their opportunities more available; their entranceways seemingly more beautiful than ever before. Blessed is the person who is prepared for such a time for there is no escaping it. “If we stay here we are safe.”  Here is how we may know that any temptation had reached its high noon and is in its hour.

First, it solicits frequent and persistent thoughts of the evil it seeks to be manifested. At first, the soul in indignation will be offended at the thoughts. But by entertaining the thoughts, the soul grows familiar with it. Instead of being startled as before, it may say, “Is it not a little one?” Then the temptation is approaching its high noon. Lust has been enticed and entangled and is ready to conceive (James 1:15).

Second, when the temptation is known to have prevailed against others, the soul is not filled with dislike and abhorrence of them and their ways. There is no pity or prayer for the other person’s deliverance. And when a temptation has been able to bring low anyone who had previously been able to prevail against it, surely its hour grows closer. “Its prevailing with others is a means to give it its hour against us.”

Third, it will complicate the situation by insinuating itself with many considerations that are not in themselves clearly evil. So it was with the Galatians and their fall from the purity of the gospel. They sought freedom from persecution as well as union and approval with the Jews. Things that were in themselves good were pleaded for, but gave life to the temptation itself.

Fourth, when its hour approaches, a temptation is restless and urgent. “It is the time of battle, and it gives the soul no rest.” Satan sees that it is now or never. So he musters his forces—the opportunities, pleas and pretences for sin. Some ground has already been taken by previous efforts. If he can do nothing now, all is lost.

Fifth, when fears and allurements are joined together, “temptation is in its hour.”  People sometimes are carried into sin by their love of it; and continue in it out of fear for what will come of it. “But in any case, where these two meet, something allures us, something affrights us, and the reasonings that run between them are ready to entangle us, then is the hour of temptation.”

This then is what it means to “enter into temptation.” And there are two means by which we are to prevent it: Watch and Pray. The first is a general expression to be on our guard; to consider all the ways and means by which an enemy could approach us (1 Corinthians 16:13).

A universal carefulness concernment and diligence, exercising itself in and by all ways and means prescribed by God, over our hearts and ways, the baits and methods of Satan, the occasions and advantages of sin in the world, that we be not entangled, is that which in this word is pressed on us.

Of prayer, Owen said he did not need to speak of it. He felt the duty of prayer was known to all. Together with being on guard, “these two comprise the whole endeavour of faith for the soul’s preservation from temptation.”

There are many areas of temptation to which John Owen’s advice can apply. But as I read this chapter, I was struck by its uncanny applicability to individuals who struggle against addiction. Lord, may they watch and pray so that they do not enter into temptation. A digital copy of Owen’s work, Of Temptation, is available here.

12/22/14

Back to the Future with Psychedelics

© Zhuxi1984 | Dreamstime.com - Back To The Future Photo

© Zhuxi1984 | Dreamstime.com – Back To The Future Photo

“I am 100 percent in favor of the intelligent use of drugs, and 1,000 percent against the thoughtless use of them, whether caffeine or LSD.” (Timothy Leary, in Chaos and Cyber Culture)

We’re going “back to the future” with recent research into the therapeutic benefits of hallucinogens for treating alcoholism and mood disorders. (See additional stories here and here; and a previous blog, “As Harmless as Aspirin?”) Classical hallucinogens such as LSD, mescaline or psilocybin, and dissociative anesthetics such as ketamine and PCP might be “useful” in the treatment of major depression, anxiety disorders and OCD. A recent study concluded: “There was evidence for a beneficial effect of LSD on alcohol misuse.” A single dose of LSD was found to be associated with a decrease in alcohol misuse. Another longitudinal study suggested that: “hallucinogens may promote alcohol and drug abstinence and prosocial behavior in a population with high rates of recidivism [with individuals on probation or parole].”

An issue of Current Drug Abuse Reviews (volume 6, number 1, 2013) was devoted to the investigation of psychedelics and their potential as therapeutic agents in the treatment of addiction. Several different articles suggested the therapeutic benefits of a variety of psychoactive substances—some classics and some newer ones.

Rick Doblin, in “Psychedelic-Assisted Psychotherapy for the Treatment of Addiction,” said: “There are multiple frameworks for understanding how psychedelic therapy can alleviate substance abuse.” He noted that the idea that psychedelics can be helpful in combating drug abuse conflicts with “the notion that psychedelic drug use is inherently wrong.”

Michael Bogenschutz of the University of New Mexico Health Sciences Center suggested that sacramental use of classic hallucinogens, like the Native American Church’s use of peyote, “is strongly associated with decreased alcohol and drug use.”

Lisa Jerome and others lobbied for studies that tested MDMA-assisted psychotherapy in people with an active substance use disorder. “It appears that MDMA, like classic psychedelics, may have a place in addressing substance abuse or dependence, which could be linked to its pharmacology or its psychological effects.”

Ayahuasca, a psychotropic brew prepared from an Amazonian vine and bush, may be associated with reduced substance use and “improvements in several cognitive and behavioral states.”

Thomas Kingsley Brown reported that ibogaine, a psychoactive alkaloid found in a rainforest shrub of West Central Africa, helps with withdrawal symptoms and reduces drug cravings..

A study of ayahuasca-assisted treatment for substance use problems by Gerald Thomas and others suggested that it was associated with significant improvements in several factors related to problematic substance use. While this particular study occurred in Canada, ayahuasca has been used as a remedy to help overcome drug addictions in Peru and Brazil. “Although these programs claim improved health outcomes for patients who complete them, neither has been evaluated with sufficient scientific rigor to provide definitive evidence of the success of their approaches.”

Ibogaine is not used in the US to treat addiction because of its severe side effects, which include hallucinations, bradycardia (slow heart rate), whole-body tremors and ataxia (lack of muscle control during voluntary movements). It also had cerebellar toxicity with high doses in rats. Nevertheless, it is a growing form of treatment outside the US. A subculture of ibogaine clinics has sprung up in Mexico. Read about a trip to one here.

A synthetic derivative of ibogaine, 18-MC, has been developed and is said to show promise. It resulted in “a long-lasting decrease in ethanol, morphine, cocaine, methamphetamine and nicotine self-administration [in rats], and attenuation [decrease] of opioid withdrawal symptoms.” Significantly, it is not expected to have hallucinogenic effects and does not have the negative side effects noted above with ibogaine.

In 2012 Savant HWP, a privately-owned pharmaceutical company in California, received a three-year grant from the National Institute on Drug Abuse (NIDA) for the pre-clinical development of 18-MC. Stanley Glick, the scientific founder of Savant and a long time researcher with ibogaine, said: “18-MC is likely to be the first of a new generation of agents effective against a broad spectrum of addictions—from hard drugs such as heroin and cocaine, to alcohol, nicotine and even sugary, high-fat foods, possibly reducing obesity rates.” On September 23rd of 2014 Savant announced they had begun human safety clinical trials on 18-MC. “Savant HWP plans to develop 18-MC as a treatment for many forms of addiction and compulsive behavior, with an initial focus on cocaine and opiate dependencies.”

The so-called “psychedelic treatment” approach, based on the original work of Humpry Osmond, uses pre and post therapeutic sessions and one large dose of your hallucinogen-of-choice (LSD, ayahuasca, psilocybin, mescaline). The spiritual, therapeutic goal is captured here by Aldous Huxley’s description of his experience with mescaline in The Doors of Perception:

The man who comes back through the Door in the Wall will never be quite the same as the man who went out. He will be wiser but less cocksure, happier but less self-satisfied, humbler in acknowledging his ignorance yet better equipped to understand the relationship of words to things, of systematic reasoning to the unfathomable Mystery which it tries, forever vainly, to comprehend.

But we should remember the warnings of Albert Hofmann, the inventor of LSD, who cautioned not to underestimate the potential negative consequences of a deliberate provocation of mystical experiences with hallucinogens like LSD. “Wrong and inappropriate use has caused LSD to become my problem child.” In the “LSD state” the boundaries between the self and the outer world effectively disappear. “A portion of the self overflows into the outer world. . . . This can be perceived as a bless[ing], or as a demonic transformation imbued with terror.”