01/31/23

Never Enough and Adaptation

In “Never Enough and No Free Lunch,” we looked at what Judith Grisel identified as the three laws of psychopharmacology from her book, Never Enough. She recalled a time when giving a brief lecture to a group of high school students on the opponent-process theory of Solomon and Corbit. A student leaped to his feet and cried out, “This changes my life!” She said she shared his sentiments and added that the theory was important because it largely “set the course” for how scientists think about and study addiction.

Richard Solomon and John Corbit proposed that every stimulus that disturbs the way we feel is counteracted by the nervous system in order to bring the body back to an emotional “set point” or homeostasis. In their description of the theory in a 1974 article for Psychological Review, “An Opponent-Process Theory of Motivation,” they said addiction did not differ in principle from any acquired motivational system. “We can easily describe opiate, alcohol, barbiturate, amphetamine, or cigarette addiction within the empirical framework of the analysis we have proposed.”

Grisel said Solomon and Corbit suggested that feeling states are maintained around a “set point” like body temperature is. Any feeling, such as being happy, depressed or excited, represents a disruption of the stable feeling state or homeostasis. The opponent-process theory suggests that “any stimulus that alters brain functioning to affect the way we feel will elicit a response by the brain that is exactly opposite to the effect of the stimulus.” The fact that our feeling states are so tightly constrained has important implications for understanding drug abuse. The brain learns by adapting to every drug that affects its function.

Some of these changes are relatively transient, like tachyphylaxis [an acute, sudden decrease of response to a drug after its administration, rendering it less effective] in an occasional drinker, but as learning is stronger with repetition, chronic exposure to a drug results in more lasting alterations. For some drugs, such as antidepressants, adaptation is actually the therapeutic point. Developing tolerance to selective serotonin reuptake inhibitors (SSRIs) may help to change a pathological affective “set point” so that being depressed is no longer the patient’s normal state. . . .As the brain adapts to a drug of abuse and the drug becomes less effective at stimulating dopamine transmission, a user must take more and more to produce the same high. Engaged in a futile attempt replicate the initial experiences, an addict repeatedly administering the drug ensures more and more adaptation.

In the following charts, the A process is what the drug does to the brain and the B process is the brain’s response or adaptation to the drug, as it attempts to return the brain to its neutral, homeostatic state. State A can be pleasant or unpleasant, but whatever it is, State B is the opposite. The set point is the line in the middle. Large doses of a drug produce large A processes, and long-lasting stimulations produce long-lasting A processes.

When the brain is first exposed to a drug, the high or A process is not initially dampened by the B process of the brain trying to return to a neutral, homeostatic state. This leads to an initial peak experience followed by a leveling off. The A process in the brain is always the same if the same amount of the drug is used, but this is not true for the B process. Generated by an adaptive nervous system, the b process learns with time and exposure. “Repeated encounters with the stimulus (or use of the drug) result in bigger, faster, and longer-lasting B processes that are better able to maintain the homeostasis in the face of further stimulation.” Another thing to know is the B process can be triggered by environmental cues that signal an A process is coming. In other words, it can trigger the A process.

After many times of getting high, an adaptation results and there is hardly a bump in the feeling (euphoric) state. The drug then functions primarily as a way to hold off withdrawal and craving in the b process, in the face of the brain’s ability to counteract the A process until drug use is stopped, then withdrawal and craving begins in earnest. The classic illustration of this is with opioids like heroin.

This model also explains why the states of withdrawal and craving from a drug are always exactly opposite to the drug’s effects. If a drug makes you feel relaxed like benzodiazepines, withdrawal and craving are experienced as anxiety and tension. If a drug helps you wake up like caffeine, adaptation includes a lack of energy and enthusiasm. If it reduces the sensation of pain like opioids do, feeling pains you didn’t know you had will happen.

The common symptoms of addiction are tolerance, withdrawal and craving, and they are embedded in the consequences of the B process. Tolerance occurs because more drug is needed to produce an A process capable of overcoming an increasingly stronger b process. Withdrawal happens because the B process outlasts the drug’s effects (see the charts above). Craving is almost guaranteed by the opponent-process model, because any environmental cue that became associated with the drug (through classical conditioning) can trigger a B process because the learning cycle or ritual that included the cue or trigger was repeated many times as the person used drugs.

This happens because of what Jeffrey Schwartz called the Quantum Zeno Effect, in You Are Not Your Brain. This means the brain areas activated by a drug are stabilized and held in place long enough so they can be wired together by Hebb’s Law. Hebb’s Law says neurons that fire together wire together. Once any sequence of neurons is wired together, the brain will respond to similar situations in a reliably “hard wired” way. So, any environmental cue that occurred repeatedly within the sequence of neurons or the ritual of “getting high” has the potential to become a trigger and initiate craving. In Never Enough, Judith Grisel gave a personal example of the incredible power of this cognitive memory process.

I was clean for close to two years and had been volunteering in my biopsychology professor’s laboratory to get some research experience. One part of the protocol required daily administration of an experimental drug into the subjects’ (rats) peritoneum, which is the sac that loosely constrains the abdominal organs. The standard procedure is to cup the rat gently in one hand, insert the needle with the other, and create negative pressure by pulling slightly back on the needle to be sure the injection isn’t going straight into a blood vessel. I thought I’d fully extinguished any personal associations by this time, but one day when I pulled back and the needle filled with blood, I heard clamorous ringing in my ears and a taste in my mouth that were characteristic of cocaine going into my vein. It was years later, in a completely different context, and I had not a whit of desire to use at that moment, but just seeing blood filling the syringe cause an instantaneous reaction. I let my colleague finish the injections and went back to my dorm sobered by the astounding power of memory.

The brain is so well organized to counteract things that cause it anxiety or unease, that it uses its learning skills to anticipate the disturbance a drug will cause rather than wait for the drug effects themselves. It starts a B process, from which you experience craving. In other words, the brain begins to dampen the drug effects before you even take the drug! So, there is a real potential for cue-induced relapse to occur and addicts need to become aware of this danger and develop a plan ahead of time, before the B process activates, to manage it if it occurs.

Originally posted on July 6, 2021

11/22/22

Brain Stimulation or Brain Damage? Part 2

On Valentine’s Day 1974, British doctors destroyed sections of Derek Hutchinson’s hypothalamus without his consent. Surgeons drilled two holes into his forehead and then sent a wire with an electrical tip deep into his brain. Before the right and left sides of the targeted area of his hypothalamus was burned for thirty seconds each, the surgeon test-stimulated his brain with five to ten volts of electricity to see whether the targeted area of his brain actually controlled emotions, and not pathways crucial to motor functions like walking, talking and breathing. They asked him if he was frightened or angry and he yelled, “Stop it, or I’ll kill you.” Then they proceeded to destroy the targeted areas of his hypothalmus.

As Danielle Egan related in her article, Derek had an hypothalomotomy, a psychosurgery procedure first developed in the 1950s to curb aggressive behavior. Over the next two decades he had repeated overdoses and hospital stays during which he received ECT. At some point, he attacked one of his psychiatrists, but no charges were filed against him. After his wife gave birth to twins, he threatened her with a gun. He met his current wife in a pub and they were married in 1982. He’s struggled with bouts of depression, impotence, insomnia, extreme fatigue and rage since the surgery. “He’s had eight heart attacks, two strokes, has battled anorexia (the hypothalamus also regulates hunger, blood pressure and hormones) and has tried to kill himself seven times.”

An MRI revealed extensive damage to his hypothalamus. They told him “Half of your hypothalamus is gone.” He said that was when he finally woke up. These days Hutchinson is an activist against the use of psychosurgeries and deep brain stimulation (DBS). He thinks psychosurgery should be banned outright and believes mental disorders are caused by an individual’s unique life experiences, and are not a product of a dysfunctional brain.

We must put an end to this immoral, unethical activity being conducted in the name of mental health research… These doctors are guinea-pigging innocent people. These surgeries should never have been invented. They kill the person and they don’t even know they’re not the same person anymore.

There are clear differences between the hypothalomotomy done to Derek Hutchinson and DBS, which seeks to electrically stimulate specific areas of the brain, not destroy them. However, the adverse effects are similar. In another article for Mad in America on DBS, Egan noted that numerous studies have documented serious adverse mood behavior and personality effects. “These include suicide, depression, apathy, fatigue, mania and serious impulse control issues, such as hypomania, aggression, addiction (to gambling, shopping, drugs, alcohol) and hypersexuality, sometimes resulting in criminal behaviour, including pedophilia.” See “Deep Brain Problems” for more on the adverse effects with DBS.

Andrew Scull described the results of two double-blind studies of DBS for depression. The first one by Dougherty et al was prompted by encouraging response rates in multiple open-label DBS trials. But there was not a significant difference in response rates between the active and control groups. “Our results … failed to demonstrate a significant difference between the active and sham-controlled groups during the blinded phase of the study.” Even worse, adverse events were more frequent in the active group than in the control group for worsening depression, insomnia, irritability, suicidal ideation, hypomania, disinhibition and mania.

There was even one completed suicide in the active treatment group. However, it occurred after the person stopped treatment because of a failure to improve and was awaiting removal of the electrodes. “The authors decided that that adverse event did not count!” Notice that the second listed author of this study, Ali Rezai, would later emerge as the lead investigator for the first U.S. clinical trial of DBS for heroin described in Part 1 of this article.

The second trial was conducted by Helen Mayberg and Andres Lozano, who are both well known supporters of DBS, and a couple dozen others. Again, there was no statistically significant difference between the stimulation group and the control group. Scull reported the researchers anticipated those receiving active stimulation would improve twice as much. Both the treatment and the placebo groups improved, but the improvement was slight and not statistically significant.

Thus, once put to a controlled test, the claims for deep brain stimulation as a treatment for depression resoundingly failed. The purely speculative and fanciful biological “theory” of depression on which the intervention rested had not produced the anticipated results.

Then in October of 2019, Mayberg published another DBS study, claiming the procedure was generally safe and well tolerated. “The rate of medical or surgical complications was consistent with the rate observed in studies of DBS for other indications.” Oh, and there were no completed suicides. Yet Andrew Scull pointed out five of the small sample of 28 individuals dropped out after 1, 2, 5, 8 and 11 years. There were 56 adverse events. One patient experienced ten of them and had the electrodes removed after two years and dropped out of the study.

What are we talking about here? Nineteen of the events involved the surgery going wrong in a variety of major ways. Six infections resulted from the brain surgery. Six patients had to have the original device “explanted,” as the authors put it, because the wires caused an infection (3 cases), failed to work (2 cases), or the crude targeting of the device needed adjusting (1 case). Another patient experienced hemorrhage of the cortex and a post-operative seizure. The device failed in 15 cases. There is no further discussion of these iatrogenic disasters, or the suffering they entailed. And then, finally, there were the serious psychiatric sequelae. Fourteen of the twenty-eight patients required re-detention in a psychiatric hospital, one on seven occasions, including five admissions occasioned by suicide attempts.

Despite the above reported adverse events, Helen Mayberg’s assessment of DBS is that it appears to be “generally safe and well tolerated.” Although the DBS studies failed to show any real efficacy with treatment-resistant depression, Mayburg concluded most participants had “a robust and sustained antidepressant response.” Andrew Scull pointed out many of the authors were indebted financially to the medical device manufacturer and that Mayburg owned patents covering the devices in question. Further, he said Mayberg et al “cherry-picked data” for their study. Positive outcomes only appeared when researchers self-assessed the results of their interventions. “Ambitious clinicians let loose in such a situation can easily be carried away by their enthusiasms, and the restraints on experimentation, while stronger than they once were, remain inadequate.”

Scull had a different take on the first-in-the-U.S. clinical trial for treatment resistant opioid use disorder described in Part 1. He pointed out the false impression given by saying the DBS device functioned much like a heart pacemaker. The human brain is not a simple pump. And despite all the progress of neuroscience over the past fifty years, our understanding of it is still primitive. “The idea of a ‘brain pacemaker’ is so ludicrous on its face as to disqualify anyone who uses it.” The analogy appears to rely on the now generally disparaged “chemical imbalance” theory of depression, as evident in the following statement:

By sending a pulsed current through the electrodes, doctors believe they can regulate an imbalance in Buckhalter’s reward circuitry.

Ali Rezai, the doctor leading the clinical trial, readily acknowledged they don’t fully understand how this works. However, they hope that by modulating the rewards circuit, which relies on the chemical messenger dopamine, “you’re getting better control, so you’re not craving dopamine as much.” This suggests DBS for opioid misuse is more explorative and experimental than it is a promising type of treatment. Scull commented: “The prattle about dopamine that he proceeds to utter as a substitute for the scientific evidence we do not possess is an embarrassment — just speculation plucked out of thin air.”

In The Science of Addiction, Carleton Erickson said scientists once held that dopamine was the “pleasure transmitter.” He said this is a simplistic explanation of severe SUD—substance use disorder. Addiction is more than seeking of pleasure or avoiding pain or withdrawal. In addition to the nucleus accumbens (part of the brain’s pleasure or reward system), recent neurobiological findings and theories extend to areas of the brain the modulate meaning and emotional and cognitive memory. “Some drugs appear to be capable of affecting these adjunctive brain areas to transition drugs from pure pleasure to habitual use to severe SUD, where pleasure or pain is no longer important in maintaining drug-taking behavior.”

Reflecting on the continuing pursuit of brain stimulation with transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS) and invasive, deep brain stimulation (DBS), I am reminded of a two-hundred-year-old novel that Mary Shelly anonymously published on January 1, 1818, The Modern Prometheus; or Frankenstein. Shelley told her story within a literary technique known as a frame narrative—a story within a story. In the frame story, Captain Robert Walton and his crew set out to explore the North Pole sometime in the 18^th century in order to expand scientific knowledge and hopefully achieve fame. They glimpsed a dog sled driven by a gigantic figure, but it disappeared into the snow. A few hours later, they found a frozen and emaciated Victor Frankenstein, who had been in pursuit of the gigantic creature.

Victor recognizes the same obsession in Walton that drove him to modern laboratory experimentation and creation of the “fiend.” As a warning to Walton, he then recounts the story of his life’s miseries that were a consequence of his obsession. With his last words, he told Walton to seek “happiness in tranquility and avoid ambition.” Let us hope that the pursuers of brain stimulation, particularly DBS, heed that counsel. Experimenting on humans by implanting electrodes into their brain to “treat” their depression or addiction seems like a similar pursuit of ambition over first doing no harm. Hopefully Derek Hutchinson’s life story and its miseries will be heard and give pause to some of these researchers.

Originally posted on February 4, 2020

10/18/22

Back to the Future with Psychedelics

© 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 also 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.”

Originally posted on December 22, 2014.

04/19/22

Recovery Is a Life-Long Process

The greatest enemy to recovery is a sense of hopelessness and helplessness: if it doesn’t seem to matter whether or not I abstain from using drugs or alcohol, why abstain? There is a similar tendency in the Christian life, as we live out the ongoing war between the desires of the Spirit and the desires of the flesh, “for these are opposed to each other, to keep you from doing the things you want to do” (Galatians 5:17). The temptation to give up, to live like a captive to the law of sin (Romans 7:23) is ever present. And the needed response in both recovery and the Christian life is spiritual tenacity or perseverance.

The importance of spiritual tenacity was emphasized in My Utmost for His Highest, for February 22^nd, “The Discipline of Spiritual Tenacity”: “It is endurance combined with the absolute certainty that what we are looking for is going to transpire.” We need to work deliberately to manifest love, justice, forgiveness and kindness to others, relying upon “the certainty that God is not going to be worsted.” We are to persevere. My Utmost for His Highest was a devotional read in early A.A.

Because of the very real correspondence between sin and addiction, spiritual tenacity or perseverance is a daily requirement for the Christian believer and the recovering alcoholic or addict. In another article, “Born of the Flesh,” I noted that addiction was simultaneously “a disease of the brain” and “an infection of the human heart.” The scientific evidence of genetics and biochemistry explains the physiological aspect of addiction, but cannot fully account for how that is translated into abnormal behavior or why the tendency to fall back into active addiction must be guarded against for a lifetime.

Increasingly in our time, materialistic cause seems to dominate accepted views of human nature and disorder. Here the bodily, material aspect of humanity is emphasized. Our mental, emotional, and spiritual lives are thought to be simply by–products of our material constitution. Therefore, explanations of human behavior have a radically naturalistic explanation. The notion of freedom, the ability to choose how we act or respond to our environment is ultimately a myth from this perspective. Moral responsibility for our actions is not something the individual can claim. Physiology, society or the environment—or a combination of these sources—is ultimately responsible for our good or bad behavior. Ultimately there is no God or Higher Power and no sin. Morality is a socially constructed phenomenon; sin does not exist; and addiction is merely a brain disease. A wonderfully complex brain disease, but ultimately caused by bio-physical mechanisms alone.

But if we are psycho-somatic beings as Anthony Hoekema claims in Created in God’s Image, we are creatures with a body (soma) and soul (psyche). Then there is an interaction between the physical and psychological aspects of our being. Genetics and biochemistry can influence human behavior, but they cannot fully determine it. If you believe that we are more than a sophisticated complex of bio-physical processes, explanations for all human behavior—including sin and addiction—must have this dual causal sense without subsuming ultimate responsibility under the other. For more on Hoekema’s idea, see “Created in the Image of God.”

Now we come to a necessary presumption, the existence of God or a Higher Power. This God or Higher Power is a necessary part of Twelve Step recovery and Christian, Biblical belief. But it is an irrelevant nuisance at best if you hold to a consistent view of addiction as merely a brain disease. When there is a God or Higher Power, there can be a basis for morality beyond human, social consensus. Wrong doing or sin can then be a violation of what this God or Higher Power declares is right. Biblical, Christian thinking goes one step further and sees sin as wrong being as well as wrong doing.

Sin is thus never merely a voluntary act of transgression; it proceeds from something more deep-seated; the expression of a sinful heart. Here the sense of sin in Romans 3:23 (all have sinned and fall short of the glory of God) and Romans 5:12-19 is in view. We are sinful in this way because the sin of Adam is imputed (credited) to all of us. Rejecting the doctrine of original sin fails to appreciate the close relationship between the imputation of Adam’s sin to all of humanity and God’s plan for the accomplishment of salvation in Christ. In the New Bible Dictionary, John Murray and B.A. Milne said:

The history of mankind is finally subsumed under two complexes, sin-condemnation-death and righteousness-justification-life. The former arises from our union with Adam, the latter from union with Christ. These are the two orbits within which we live and move. God’s government of men is directed in terms of these relationships. If we do not reckon with Adam we are thereby excluded from a proper understanding of Christ. All who die die in Adam; all who are made alive are made alive in Christ.

So that which is born of the flesh (the physical body) is flesh (a depraved heart, given over to wickedness). Addiction is simultaneously a disease of the brain and an infection of the heart. And this bio-psycho-social-spiritual ‘disease’ precedes the addictive/sin behavior noted in Romans 7:18-19: “For I have the desire to do what is right, but not the ability to carry it out. For I do not do the good I want, but the evil I do not want is what I keep on doing.”

Like sin, addiction is wrong being as well as wrong doing. And the wrong being of addiction has an ongoing existence in the human heart that continually strives to re-engage the addict or alcoholic in the wrong doing of active drinking or drug use. So, it’s not enough to simply abstain from drugs or alcohol; the addict has to change: Abstinence plus change equals recovery. And this change process must be a lifelong pursuit.

Walking Up the Down Escalator

One metaphoric image that captures this truth is to say that recovery is like walking up a down escalator. The trick for progress is to continue walking up the escalator faster than it is moving down. It doesn’t matter how long you have been walking up the escalator, the moment your efforts to walk up are less than the down movement of the escalator, you start to drift back to where you started. You may even continue to walk up; but if the effort isn’t greater than the movement of the down escalator, you don’t even realize you are actually moving backwards. For more on this concept, see “Preventing the Relapse Process, Part 2.”

In the AA Grapevine article, “PO Box 1980,” was the story of an older man at a treatment center. He approached a counselor after a talk on relapse and said that until two weeks before that, he had been sober for forty-two years. For thirty-nine of them, he attended A.A. meetings. After he moved three years ago, he stopped going to A.A. when he found that he just didn’t like the meetings in his new area. He figured he’d heard all he was going to hear and learned all he was going to learn; that he didn’t need them after thirty-nine years.

On an ordinary day, when a couple of things went wrong, he thought he would feel better with a drink. “That first day I only had a couple, but the next day I drank until I passed out. I disappeared for two weeks and my grandkids came looking for me. They found me passed out in a closet and they brought me here.” Abstinence relieves the symptoms of wrong doing, but it does not cure the disease of addictive wrong being. Recovery is a life-long process.

If you’re interested, more articles from this series can be found under the link for “The Romans Road of Recovery.” “A Common Spiritual Path” (01) and “The Romans Road of Recovery” (02) will introduce this series of articles. If you began by reading one that came from the middle or the end of the series, try reading them before reading others. Follow the numerical listing of the articles (i.e., 01, 02, or 1st, 2nd, etc.), if you want to read them in the order they were originally intended. This article is the 12^th in the series. Enjoy.

11/16/15

A Blood Test for Addiction?

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

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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.

Faith Seeking Understanding

Charles Sigler, D.Phil.

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