Addiction, Alcoholism, Naltrexone, Sinclair method, Oxytocin, Baclofen, Suboxone

The End of Addiction?

K. Paul Stoller, MD, FACHM

Alcoholism affects more than 27 million Americans. In a world where less than 10% of those with alcohol addiction are getting treatment, one of the conditions most satisfying to treat is alcohol use disorder (AUD).

Suboxone

Addiction medicine hasn’t changed for a long time with the exception of the introduction of Suboxone—an opioid buprenorphine in combination with naloxone. Naloxone, frequently referred to as Narcan, is an opioid receptor antagonist that effectively occupies the human opioid receptors but blocks any action. Suboxone is one of the primary pharmaceuticals used today in medication-assisted therapy (MAT) for opiate addiction.

Suboxone obviously helps with neurotransmitter aspects of an opioid addiction because it is an opioid that provides a short-term fix that makes it easier to adapt to long-term treatment. If one is choosing between Suboxone and doing nothing, then Suboxone is a better choice. But it is not real addiction treatment for opioid addiction, let alone any other kind of addiction.

The process of addiction–and the underlying disorder that addiction mitigates—is the actual problem. Opioids, nicotine, cocaine, or alcohol are ultimately a form of self-medication—just the means to an end.

Naltrexone and the Sinclair Method

Naltrexone is a treatment option that was introduced in the 1960s and is used in the Sinclair method as a stand-alone drug for alcohol addiction treatment. The medication reduces opioid effects by competing for opiate receptors and displacing opioid drugs from these receptors, reversing their effects. The metabolite of naltrexone, 6β-naltrexol, is also an active agonist. Consequently, the effects of naltrexone arise from both the parent drug and its major metabolite and last about a day It is capable of antagonizing all four types of opiate receptors.

AUD patients prescribed naltrexone take the medication orally about an hour (and only then) before drinking, blocking the positive-reinforcement effects of alcohol, which allows the person to stop or reduce drinking (the Sinclair method). This occurs because for an alcohol addict, drinking causes massive release of dopamine and endorphins, the source of intense craving for alcohol—even years after being sober. Alcohol also increases the activity of GABA (γ-aminobutyric acid), a major inhibitory neurotransmitter in the brain that suppresses activity of the central nervous system with accompanying calmative effects.

This opioid blocker is intended to reduce and eventually erase habit-forming behaviors, diminishing a person’s craving for alcohol to its pre-addiction state. This assumes that the primary underlying dynamics in alcohol addiction are habit and conditioned response. However, the limited success of naltrexone alone makes it clear that more complex neurochemical and genetic factors are involved.

Naltrexone and naloxone differ in their utility in addiction treatment. Naloxone is effective in opioid overdose rescues, acting within minutes to reduce opioid levels, which lasts for about an hour because of rapid metabolism. The different half-life of naltrexone and naloxone explains why the two drugs have different purposes. Naltrexone is used to block cravings for both opioids and alcohol, but naloxone is not; naloxone can treat overdoses but naltrexone cannot. Both drugs block the analgesic action of both exogenous opioids and the pleasure response of endogenous endorphins, but naloxone acts quickly enough to treat an overdose while naltrexone does not. For these same reasons, naltrexone cannot be used to rescue someone from an overdose but can be used to help people who are addicted to opioids have less craving for them.

However, I have never used naltrexone to treat addictions. Rather, I use the bio-identical hormone oxytocin to achieve the same effect, because it also sits on the body’s opioid receptors, is capable of putting opioid addicts into withdrawal, and has agonist action comparable to naltrexone.

Oxytocin

No one, as far as I know, has compared oxytocin to naltrexone; but naltrexone is considered only modestly successful at treating AUD, and oxytocin by itself has had only modest success in my clinical experience. Consequently, I do not use oxytocin alone for AUD because it does not get the job done. Modest success is not satisfactory.

Initially, I started using oxytocin because it helped my brain-injured patients deal with the PTSD that comes along for free when one has a stroke, TBI, or some other form of brain injury. As the brain heals and one becomes more aware of how messed up life is, that can cause a great of anger and anxiety; the oxytocin blocks inappropriate fear and panic from engaging the limbic area of the brain. It even seems to help the brain process more effectively. When I learned that one of the effects of drinking alcohol is to increase oxytocin levels, I thought it was worth a trial to use it in alcohol cessation. However, while oxytocin may be a secondary gain from drinking alcohol, oxytocin-seeking is not the driving mechanism of the addiction.

Rather, I believe that the ultimate hook in alcoholism is the endorphin explosion that those prone to addiction experience. Without this endorphin explosion in individuals with the wrong constitution or genetics, there would be no craving and no addiction.

Baclofen

This brings us to the classic drug baclofen. Without getting too technical, the mesocorticolimbic (MCL) dopamine (DA) system plays a critical role in mediating the positive reinforcing effects of a variety of abused drugs, including cocaine, amphetamine, nicotine, and opiates.^{1 2 3} This anatomical pathway originates from the ventral tegmental area (VTA) in the midbrain and projects to several forebrain regions, including the nucleus accumbens (NAcc) and medial prefrontal cortex (mPFC).^3,4

Since opiate receptor activation generally inhibits individual neurons, opiate-induced DA release was initially hypothesized to be mediated by a disinhibitory mechanism, i.e. opiates inhibit VTA GABAergic interneurons to decrease GABA release, which subsequently disinhibits VTA DA neurons, leading to an increase in NAcc DA release.⁵ The mesolimbic DA system may be the substrate upon which opiates act to produce their reinforcing effects.⁶ One could then postulate that if GABA is provided in therapeutic amounts, the VTA DA neurons will not become disinhibited.

Baclofen has already distinguished itself in the medical literature for utility in treating AUD (when the dose is allowed to be titrated up to whatever level a patient needs to obtain control). This point bears repeating because the medical literature is replete with randomized trials showing that baclofen does not work; but when you consider the dose used in the trials, it was inadequate. It is only when the patient is allowed to slowly titrate the dose up without limit that one sees the desired effect.⁷ Be that as it may, the mixed results from studies with suboptimal doses have stifled baclofen’s utilization for treating addictions, specifically in AUD. A double-blind RCT using baclofen for cigarette cessation published in 2015 was successful at 20 mg four times a day.⁸ Still, that dose is usually far too low for AUD. The logistical issue is that there are very few physicians who will give an AUD patient the opportunity to try baclofen because they have no training in using it for AUD, let alone using it with potentially high-dose titration. It is noteworthy that not all AUD patients need high dose levels, but many do. This all makes sense if you understand that as a GABA agonist, baclofen seems to prevent the disinhibition of the VTA DA neurons (i.e. inhibiting dopamine production), so there is no reinforcement for the addictive behavior.

CBD

This brings us to CBD. Discrete disturbances of AMPA GluR1 and cannabinoid type-1 receptor expression, observed in the NAcc, associated with stimulus cue-induced heroin-seeking, were normalized by CBD treatment.⁹ CBDs can be initiated at full dose out of the starting gate—there is no need to wait to bring up the baclofen dose to therapeutic levels (however long that takes). Between baclofen and CBD, the VTA DA neurons remain inhibited and oxytocin is just icing on the cake—the endorphin cake—by inhibiting a release that would only serve to reinforce the addictive behavior and by supporting a sense of wellbeing.

Protocol

These three relatively benign medications in tandem support an affordable, effective intervention in which the mechanisms for eliminating addiction reinforcement are relatively well understood and well-documented.

• Baclofen.

  I start patients off at a very low dosage of baclofen because some people are very sensitive, so we begin at 5 mg twice a day. I have them slowly increase their dose to 20 mg QID. This is the dosage that was used in the cigarette trial. One has to increase the dose slowly while the patient acclimates to the somnambulistic quality of baclofen. However, as pointed out, that dose is usually inadequate for AUD.

Caution in weaning.

It is also important to wean off the baclofen slowly. This is absolutely not a drug that can be quit cold turkey. Reported potential side effects of abrupt weaning include hallucinations and seizures.¹⁰

• CBD.

  The required dose of CBD is 40 mg QID.

• Oxytocin.

  The oxytocin cannot be used until the patient is sober because that will put people with opioid addiction into withdrawal. Once they are sober, sublingual troches of 25 mg of oxytocin, used up to four times a day, complete the protocol.

• Contraindications.

  Note that oxytocin cannot be given to pregnant women. Patients with brain injuries, stealth brain infections such as Lyme or cytomegalovirus, or severe dementia may not be good candidates for this protocol.

Nothing works 100% of the time on 100% of people. For the majority of patients, this protocol has great potential and is relatively inexpensive. Oxytocin 25 mg troches can be purchased (via compounding pharmacies) for less than a dollar/day in most cases, so perhaps $3/day at maximum dosage. CBD can vary widely in price, but a fair price is $60 for an ounce tincture in which one drop is 1 mg, so at maximum dose, the cost is $120 per week. Baclofen is sold for pennies a tablet. The cost is about $500 per month for this protocol. How long anyone stays on the protocol is between him or her and their physician

.

Addiction management is ultimately very individualized. If the patient needs a high dose of baclofen, it can take a couple of months to ramp up the dose to a helpful level. While I let folks wean themselves off baclofen when they no longer need it, I encourage them to take the CBD and oxytocin ongoing. These are benign calmatives. Additionally, the patient can always reintroduce the baclofen if they need it.

Discussion

While naltrexone, used in the Sinclair method, is only $50 a month if insurance is covering the medication, in my experience it does not work for everyone. While the naltrexone prevents the endorphin explosion after drinking, it does not help brain processes that are mitigated by oxytocin.

Naltrexone also does not deal with the ongoing cravings (psychological) that many experience for a lifetime afterward, even after years of sobriety. The naltrexone only blocks secondary gain (dopamine and endorphin release) at the moment of imbibing. Additionally, naltrexone is not effective for addiction to cigarettes, cocaine, or other substances. Those prone to addiction get addicted to all sorts of things. Ultimately it is the underlying addiction chemistry itself that we need to address.

Addiction treatment using Suboxone can take two years, serving as a bridge while one is doing other things in their life to cope with the addiction. The medication often only works when it is taken consistently. It doesn’t really move the gauge, just keeps the gauge from going into the red zone.

To date, no one has published on the clinical use of baclofen and CBD in combination with oxytocin for addiction mitigation. Nevertheless, I do not expect that what I just revealed will change the face of addiction medicine. In fact, it is not a problem limited to addiction medicine, it is ubiquitous through the entire medical paradigm. If a medication or an intervention is not going to make a profit for a corporation that can adequately promote, market, and educate the medical community, no one is going to hear about it, let alone use it.

My problem is that pharmaceutical companies will sit on useful medical knowledge they could share, but do not share, because they either will not profit from it or because that knowledge will interfere with the marketing of something they want sold. The corporate control of medicine is so endemic, most physicians have no idea their clinical choices are controlled and truncated by corporations, not science. It is a regrettable situation when so many are needlessly suffering, and there are potential solutions for them.

K. Paul Stoller, MD,

is a fellow of the American College of Hyperbaric Medicine and has an integrative medical practice in Santa Rosa, California. A pediatrician, he has documented the effectiveness of hyperbaric oxygen in reversing fetal alcohol syndrome in children (Pediatrics, 2005). He began working with patients of all ages with brain disorders in the late 1990s, including traumatic brain injury, stroke, cerebral palsy, multiple sclerosis, chemo-brain, autism, and Lyme. He is author of the book, Incurable Me: Why the best medical research never makes it into clinical practice (New York, Skyhorse, 2016).

Dr. Stoller is available remotely for medical consultations, including consults on addiction medicine. Website: www.hbotsf.org