Medication-Assisted Treatment

Methadone Maintenance Treatment (MMT), which is included under the umbrella of Medication-Assisted Treatment (MAT), substitutes methadone – a synthetic long-acting opiate, for other shorter-acting opiates such as heroin. It is administered over a prolonged period of time, possibly indefinitely, as a ‘harm reduction’ strategy for an individual who is dependent on other, mostly illicit, opioids.

It works by maintaining the level of opioids in an individual’s system, thereby avoiding the uncomfortable withdrawal symptoms associated with abstinence. Because methadone is long acting it need be administered only once a day to suppress withdrawal symptoms, thereby making it an ideal drug for managing an individual’s opioid dependence in a much more stable and predictable manner than shorter acting opioids, which wear off quickly and oftentimes must be used several times each day to stave off withdrawal symptoms.

Similar to heroin, methadone patients can overdose on methadone, develop physical dependence after continued use, and undergo severe withdrawal if they stop using abruptly without a gradual tapering off period. In fact, methadone withdrawal has been known to be fatal if left untreated. Methadone patients who have been incarcerated without access to quality medical attention have died of dehydration when they are not able to retain enough fluids in their body as a result of extreme vomiting and diarrhea.

The theory behind this treatment method is that patients are able to resume normal daily functioning and eventually taper off the medication when they have established functional patterns and habits in their life. It is used as a replacement for heroin, simply because it does not engender the destructive lifestyle that heroin users often experience when attempting to attain, manage and control a substance that is illegal and must be obtained through illegal channels. Because it is a controlled substance, methadone is regulated by the Drug Enforcement Administration (DEA) and is only available at government regulated clinics, where patients can get small amounts – typically only enough to get them through one day. Patients, therefore, must visit the clinic every day, in order to maintain their treatment protocol.

The downside is that in many cases it fails to resolve the problem of opiate addiction. Many clients never fully abstain from using illicit opiates or other drugs while in treatment. Concurrent heroin use is a common phenomenon among MMT clients, and it subsequently exposes them to a greater risk. Yet, the MMT program providers often prefer to ignore this because ceasing treatment for continued drug use is associated with higher overdose death. Concurrent heroin and benzodiazepine use among MMT clients is a long-standing and broadly recognized phenomenon worldwide, despite the fact that these combinations can be lethal (Luo et al, 2016).

Knowledge of these risks, without appropriate intervention, is not a sufficient response. As evidenced by the many cases of methadone-related deaths, clinicians are aware of the patient’s history of polysubstance abuse or dependence. The issue of comorbid substances is not adequately addressed in MMT, and no specialized treatment plans for these patients are defined and implemented. (Rosic et al, 2017)

BENEFITS

• MMT allows patients to safely manage their disorder and to choose the most suitable time (if ever) for weaning off opiates (Bonhomme et al, 2012; Cao et al, 2013; Ducharme et al, 2012; Garcia-Portilla et al, 2012; Hser et al, 2016; Mattick et al, 2009; Veilleux et al, 2010)
• Alleviates opioid withdrawal symptoms and “cravings” associated with abstinence from opioids (Bonhomme et al, 2012; Ducharme et al, 2012; Garcia-Portilla et al, 2012; Veilleux et al, 2010)
• Statistically significant improvements in quality of life (Kobra et al, 2007; Marinković et al, 2017), and improvements in illicit opioid use and psychiatric status between the 3rd and 12th months (and beyond) as patients ‘stabilize’ on the medication (Maremmani et al, 2007)

RISKS

• A relatively large proportion of those engaged in treatment (20%-75%) continue to demonstrate on-going drug use –most notably heroin (40%-60%), benzodiazepines (20%-37%), and cocaine(Ainscough et al, 2017; Baumeister et al, 2014; Brooner et al, 2013; Cohen et al, 2005; Curcio, 2011; Dobler-Mikola et al, 2005; Dunn et al, 2008; Ernst et al, 2002; Flynn et al, 2003; Hoang et al, 2018; Jimenez-Treviño et al, 2011; Kamal et al, 2007; Leavitt, 2005; Lee et al, 2014; Li et al, 2012; Luo, 2016; Mouly, 2014; Naji, 2016; Nielsen et al, 2015; Pinto et al, 2010; Reece, 2007; Rosic et al, 2017; Roux et al, 2016; Sees, 2000; Soyka, 2008, 2017; Taylor, 2015; Wang et al, 2014; Wasserman et al, 1999)
• Highest death rate of any opiate –2X as many as OxyContin (CDC, 2012; Szalavitz, 2012) and associated with one-third of opioid-related overdose deaths annually (Thomas, 2014)
• MMT patients are at a higher risk of death from drug overdose even when under the care of a methadone treatment provider (Bell et al, 2009; Best et al, 2009; Bonhomme et al, 2012; Cao et al, 2013; Ernst et al, 2002; Gibson and Degenhardt, 2007; Huang and Lee, 2013; Jimenez-Treviño et al, 2011; Maxwell et al, 2005; Nielsen et al, 2015; Qidwai, 2015; Reingardiene et al, 2009; Rosic et al, 2017; SAHMSA, 2010; Sordo et al, 2017; Zador and Sunjic, 2000)
• Dangerous and/or fatal interactions with other prescribed drugs –such as benzodiazepines /antianxiety medications (CDC, 2012; Ernst et al, 2002; Fields et al, 2015; Lee et al, 2014; Rosic et al, 2017; Shields et al, 2007; Thomas, 2014)
• Toxicity deaths from diverted methadone (not prescribed to the decedent) represent a sizeable percent of all methadone-related deaths (Karch and Stephens, 2000; Shields et al, 2007)
• Causes major and sometimes fatal irregularities and disturbances of cardiac rhythm (Alinejad et al, 2015; CDC, 2012; Soyka, 2017)
• Has a black box warning for increased risk of respiratory depression and prolonged intervals between heartbeats –both of which are potentially fatal conditions, particularly during treatment initiation and dose titration (O’Shea, 2015; Soyka, 2017; Thomas, 2014)
• MMT patients have a significantly higher Emergency Room admission rate than patients treated with buprenorphine, oral naltrexone, or extended-release naltrexone (Vivitrol) (Baser et al, 2011)
• Suicidal ideation is particularly high among MMT patients (Best, et al, 2009; Darke and Ross, 2001; Ernst et al, 2002; Hubbard et al, 1997; Soyka, 2017)
• MMT has been linked to impaired cognitive function in a 2013 systematic review of 35 published scientific studies (Wang et al, 2013)
• MMT has been linked to neuropsychological deficits (Davis et al, 2002; Mintzer et al, 2004)
• MMT has been linked to slower cognitive processing, lower attention spans and lower cognitive flexibility, as well as less accuracy on working memory and analogical reasoning than former heroin users who have abstained from using any substances (Rapeli et al, 2011; Verdejo et al, 2005), or who have been maintained on Vivitrol (Rapeli et al, 2011)
• MMT has been linked to lower scores on emotion perception and social inference than former heroin users who have abstained from using any substances (McDonald et al, 2012)
• MMT has been linked to suppressed testosterone levels associated with erectile dysfunction, fatigue, and mood disturbances (Al-Gommer et al, 2007; Bawor, 2014; Bonhomme et al, 2012; Deyo, 2013; Fooladi et al, 2016; Hosseini  et al, 2013; McMaster University, 2014; Tatari et al, 2014; Yee, 2016) in up to 65% of MMT patients (Teoh et al, 2016; Zafarghandi et al, 2016)
• Suppressed fetal heart rate and less motor activity detected for babies in utero following medication dosing of mothers (Alinejad et al, 2015; Jansson et al, 2011; Salisbury et al, 2012)
• High risk of Neonatal Abstinence Syndrome (NAS) when used during pregnancy (Bonhomme et al, 2012; Gaalema et al, 2012; Jansson et al, 2011; Jones, 2010; Keough and Fantasia, 2017; Qidwai, 2015; Thomas, 2014), with 77.8% methadone-exposed newborns exhibiting severe NAS, and 52.8% needing treatment (Kakko, Heilig and Sarman, 2008)
• Severe withdrawal symptoms, at times leading to death –caused by dehydration (Gryczynski et al, 2013; Uebelacker, 2017)
• Patients’ frequently combine clonidine with methadone to get ‘high’.
• Users report: ineffectiveness in suppressing heroin cravings, intensification of cravings for other drugs, deterioration of teeth and bones, swelling, over-sedation, skin discoloration, stomach problems, internal bleeding, weight gain, sagging skin, irritability, sleepwalking, negative effects on posture, loss of bodily control, decreased economic productivity, addiction to methadone, and worry about death (Gryczynski et al, 2013), and perceive it as being the “least safe, least efficacious, and least consistent with being drug-free of all the MATs” that are approved by the FDA (Uebelacker, 2017)

Levacetylmethadol is a synthetic opioid similar in structure to methadone. It was approved in 1993 for the treatment of opioid dependence, but was removed from both the European market (in 2001) and the U.S. market in (2003) due to reports of life-threatening ventricular rhythm disorders. Unlike methadone, which requires daily administration, LAAM was administered two to three times a week. Take-home doses were never prescribed. It provided an advantage for patients who were unable to travel long distances to a methadone clinic each day. Because LAAM has a long half-life, withdrawal symptoms were delayed and known to be less severe than with other opioid medications.

Buprenorphine, like methadone, is an opiate used as a replacement drug for heroin or other stronger opiates as a harm reduction measure –gradually tapering a patient off opiates to avoid the effects of sudden and severe withdrawal.  Patients who have been dependent upon stronger opioids, like heroin, methadone, or Oxycodone, do not feel ‘high’ from the lower dose opioid –but it works just enough so that they do not feel sick.  The cravings experienced in post-acute opioid withdrawal are significantly reduced or eliminated.  It also blocks the effects of other opioids –so that a patient cannot get ‘high’ if they do use other opiates.  Buprenorphine, unlike other opioids, including methadone, is not strong enough to cause the patient to overdose.

Currently, buprenorphine is the primary active ingredient in four main products used for opioid maintenance therapy: Suboxone, Zubsolve, Subutex, and Probuphine.

• Both Suboxone and Zubsolve, include Naloxone –an additional medication that works to deter abuse by causing a patient to experience severe and immediate withdrawal if the patient uses other stronger opiates, or if they inject the product, rather than take it sublingually (under the tongue), as directed.  Subutex does not include this active ingredient.  This is because some patients experience nausea and/or vomiting as a result of the Naloxone.  Until recently, all forms of buprenorphine products had to be taken daily –either by pill or strip, placed under the tongue until it dissolved.
• Probuphine is a six month slow-release buprenorphine implant drug that was approved for medical use by the FDA in May, 2016.  It produces the same effects that the daily oral dose does.  Four one-inch-long rods are implanted under the skin on the inside of the upper arm and provide treatment for six months.  Administering Probuphine requires specific training because it must be surgically inserted and removed.  Health care providers must complete specific training and become certified in order to administer the treatment.

Note: The Controlled Substances Act requires office-based physicians prescribing buprenorphine in the United States to either refer patients to behavioral treatment or provide it themselves. However, there is no evidence as to which behavioral therapies, if any, actually work to benefit the patient. (Amato, 2011; Ling et al, 2013; Thomas, 2014)

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A Word about Buprenorphine Diversion

Although a frequently diverted medication (Addiction Treatment Forum, 2011; Cicero and Inciardi, 2007; Johnson and Richert, 2015; Sansone and Sansone, 2015; Soyka, 2014; University of Maryland, 2011; Winstock, Lea and Sheridan, 2007; Wish et al, 2012) –with as many as 24% of patients diverting their medication in the past year (Winstock, Lea and Sheridan, 2007), and as many as 68% diverting their prescriptions at some point (Johnson and Richert, 2014). Despite these statistics, buprenorphine still has one of the lowest diversion rates of any other opioid (Soyka, 2014; Yokell, 2011).

According to surveys of drug users, it is diverted primarily to prevent withdrawal or to wean off heroin –80% (Alho et al, 2007; Bazazi, 2011; Cicero and Inciardi, 2005; Kenney et al, 2017; Mitchell et al, 2009; Yokell, 2011) –84% of patients view diversion as mostly positive, and 77% of patients perceive that it is the “morally right” thing to do for a friend who is ‘dope-sick’ (Johnson and Richert, 2015). Only about one fifth (20%) of those surveyed report that diverted buprenorphine is used to get ‘high’ (University of Maryland, 2011; Wish et al, 2012). Thus, diversion may reflect lack of access to MAT treatment when not otherwise available (Addiction Treatment Forum, 2011; Alho et al, 2007; Bazazi, 2011; Fox et al, 2015; Kenney et al, 2017; Lofwal and Havens, 2012; Maxwell, 2006), including among inmate populations (Addiction Treatment Forum, 2011; University of Maryland, 2011; Wish et al, 2012). For those using ‘street bupe’ to taper off of heroin or methadone dependence, there are online resource and support groups to facilitate self-treatment and provide medical advice.

Contributors to discussion boards seem to trust each other more than they trust pharmacists and prescribing physicians. (Brown and Altice, 2014)

Conversely, 40% of clinicians believe that buprenorphine diversion is a “dangerous problem”, while those clinicians with greater [buprenorphine] patient experience are more likely to believe treatment access barriers are the major cause of diversion. (Schuman-Olivier et al, 2013; Soyka, 2014)

Interestingly, many patients with prior illicit buprenorphine use may be inclined to seek buprenorphine treatment (Gryczynski et al, 2013) and have significantly higher odds of remaining in treatment through six months than patients who are naïve to the medication upon treatment entry (Monico et al, 2015).

 

BENEFITS

• Mitigates withdrawal symptoms and, except for Subutex (which does not contain Naloxone), blocks the ‘high’ effects of other opioids (Bonhomme et al, 2012; Ducharme et al, 2012; Dupouy et al, 2017; Garcia-Portilla et al, 2012; Hser et al, 2016; Ling and Wesson, 2003; Mattick et al, 2014; Maxwell, 2006; Nutt, 2014; Sittambalam et al, 2014; Veilleux et al, 2010; Walsh and Eissenberg, 2003)
• Statistically significant increases in patient-perceived mental, physical, and emotional health, and improvements in overall quality of life (Kobra et al, 2007; Marinković et al, 2017; Parran et al, 2010: Sittambalam et al, 2014), and improvements in illicit opioid use and psychiatric status between the 3rd and 12th months as patients ‘stabilize’ on the medication (Maremmani et al, 2007)
• At a 3.5 year follow-up of patients who had been maintained on buprenorphine, 32% had tapered off and were opioid free, 29% were still on buprenorphine maintenance without any illicit opioid use, 8% were receiving maintenance treatment while using illicit opioids, and the remaining 31%had relapsed, left treatment and were using illicit opioids –thus slightly less than two thirds had successfully ended their illicit opioid use (Weiss et al, 2015)
• Potential for rapid stabilization and transferal to other treatment modalities, including naltrexone (Vivitrol) or abstinence-based therapies (Nutt, 2014; Seifert et al, 2002; Veilleux et al, 2010)
• Less likely to cause respiratory depression and overdose death then methadone (Bell et al, 2009; Bonhomme et al, 2012; Lee et al, 2013; Qidwai, 2015; Sittambalam et al, 2014; Soyka, 2017; Teruya et.al, 2014; Thomas, 2014; University of Maryland, 2011)
• Although Buprenorphine patients are more likely to discontinue treatment within the first 50 days then methadone patients  (Bonhomme et al, 2012; Mattick et al, 2008), this is not associated with a higher risk of death than methadone (Bell et al, 2009)
• Withdrawal symptoms are less severe than methadone because there is less physical dependence(Bonhomme et al, 2012; Gryczynski et al, 2013; Kosten et al, 1991; Sittambalam et al, 2014; University of Maryland, 2011)
• Does not have the same sedating effect as methadone –which many patients find preferable(Gryczynski et al, 2013)
• Less impact on male testosterone levels than methadone –significantly less reports of sexual dysfunction (Al-Gommer et al, 2007)
• The unborn fetuses of mothers treated with buprenorphine have better biophysical profile scores, more movement, less fetal heart rate suppression, and less overall disruption to their developing neural system than mothers dosed with methadone (Jansson et al, 2011; Salisbury et al, 2012)
• Lower risk of Neonatal Abstinence Syndrome (NAS) than methadone when used during pregnancy (Bonhomme et al, 2012; Gaalema et al, 2012; Hancock, 2017; Jones et al, 2010, 2012; Kakko et al, 2008; Keough and Fantasia, 2017; Minozzi et al, 2013; Qidwai, 2015; Unger et al, 2012).  In one study, mild neonatal abstinence syndrome occurred in 40.4% of buprenorphine-exposed infants with only 14.9% needing treatment, compared with 77.8% of methadone-exposed newborns exhibiting severe NAS, and 52.8% needing treatment (Kakko et al, 2008). Methadone-exposed newborns remained in the hospital an additional week longer than those exposed to buprenorphine (Jones, 2010)
• Moderately strong evidence indicates a lower risk of preterm birth, greater birth weight and larger head circumference with buprenorphine treatment of mothers during pregnancy compared with methadone treatment (Keough and Fantasia, 2017; Zedler et al, 2016)
• Buprenorphine exposed newborns had superior neurobehavioral scores and less severe withdrawal than methadone-exposed newborns (Coyle and Salisbury, 2012)
• More accessible than methadone clinics for patients in rural areas due to the ability to receive take-home doses (Hancock, 2017; Thomas, 2014)

RISKS

• Difficulties in tapering patients off due to long-lasting withdrawal effects (Bonhomme et al, 2012; Seale et al, 2014), and subsequent risk of overdose (Dupouy et al, 2017)
• Tapering off buprenorphine after taking it for less than 1-3 months is attributed to high relapse rates and increased risk of overdose death (Bonhomme et al, 2012; Flellin et al, 2014; Woody, 2008). Studies report only a 7%-9% abstinence rate at 2 month follow-up for this ‘short-taper’ protocol(University of Maryland, 2011; Weiss et al, 2011; Weiss and Rao, 2017)
• Patients leaving treatment early without effectively tapering down to gradually lowered amounts are at greater risk of relapse.  Patients have attributed leaving treatment to conflicts with staff, involuntary discharge, and perceived inflexibility of the program (Gryczynski et al, 2014)
• Abuse potential exists –tablets can be crushed and snorted or injected (Addiction Treatment Forum, 2011; Cicero and Inciardi, 2007; Johnson and Richert, 2015; Sansone and Sansone, 2015; Soyka, 2014; University of Maryland, 2011; Winstock et al, 2007; Wish et al, 2012). Patients’ can enhance the ‘high’ effects by combining it with amitryptyline, clonidine, or gabapentin (Seale et al, 2014)
• Risk of Neonatal Abstinence Syndrome (NAS) for newborns of mothers treated with buprenorphine (Bonhomme et al, 2012; Gaalema et al, 2012; Hancock, 2017; Jansson et al, 2011, 2017; Jones et al, 2010, 2012; Kakko et al, 2008; Keough and Fantasia, 2017; Minozzi et al, 2013; O’Connor et al, 2011; Qidwai, 2015; Salisbury et al, 2012; Unger et al, 2012).  Also reduces fetal heart rate and rate variability, and heart rate accelerations directly following the mother’s dosing (Jansson et al, 2017).

Naltrexone is an opioid-blocker with relatively few side effects. Vivitrol, approved in 2010, is the brand name for the sustained-release injectable form of Naltrexone and is administered via a monthly injection by a medical practitioner. Prior to 2010, Naltrexone pills had to be taken daily by the patient. The Vivitrol shot allows naltrexone to be gradually released into the body over the course of a month, at which time the patient must return for their next injection. This medication, unlike methadone or buprenorphine, is not an opiate and produces no euphoric effect. As such, there are also no withdrawal symptoms.

Both forms of naltrexone delivery (oral and injection) reduce or eliminate cravings associated with opioid dependence, and also block the opioid receptors so that the individual is unable to feel the expected ‘high’ if opioids are self-administered. The theory behind the treatment is that the individual will refrain from using opiates, even when they experience cravings because they know they won’t feel the expected euphoria associated with their former drug use experience. Even for those patients who “test the blockade” by using opiates while also getting the Vivitrol shot, they typically remain opiate-free after this initial experimentation if they continue with naltrexone therapy. The repeated lack of the desired opioid effect –the ‘high’, as well as the perceived futility of using opiates, will gradually result in breaking the habit of opioid dependence. The idea is to remain on naltrexone treatment until opioid cravings and other post-acute withdrawal symptoms have dissipated over time.

This choice is ideal for patients who are not interested in opioid maintenance therapy or long-term residential treatment, who are being treated in settings or under circumstances where these treatments are not available, or who are currently receiving opioid maintenance therapy but no longer wish to be dependent on opioids (buprenorphine or methadone) at all. In one study, more than half of current opioid users seeking treatment were ‘very’ or ‘quite’ interested in trying Vivitrol for a year, while less than a quarter were ‘not interested’ at all (Haase et al, 2016).

BENEFITS

• A viable option for patients who wish to abstain from opiate use –including maintenance medications (Brooks et al, 2010; Dean et al, 2005; Fishman, 2010; Gastfriend, 2011; Hartung et al, 2014; Hulse, 2010; Krupitsky et al, 2010, 2011; Kunoe et al, 2009, 2012, 2014; Lee et al, 2015, 2016; Lobmaier, 2010; Mogali, 2015; Ndegwa et al, 2017; Reece, 2007; Sigmon et al, 2012; Sullivan et al, 2015)
• Non-controlled substance with no known abuse or diversion potential (Lee et al, 2016; Mannelli et al, 2011; Ndegwa et al, 2017)
• Produces no euphoria or sedation, is not addictive, and has no withdrawal symptoms upon cessation (Comer et al, 2006; Kjome and Moeller, 2011; Krupitsky et al, 2010, 2011; Ndegwa et al, 2017; Reece, 2007)
• Improvement in employment status and reduction of legal and social problems are associated with continued use (Kjome and Moeller, 2011)
• Effective in preventing craving and relapse among patients (Comer et al, 2006; Gastfriend, 2011; Hulse, 2010; Kjome and Moeller, 2011; Krupitsky et al, 2010, 2011; Kunoe et al, 2012; Lee et al, 2016; Ndegwa et al, 2017; Reece, 2007)
• Patients receiving sustained-release naltrexone remain in treatment longer than those receiving oral naltrexone or no medications following detox (Brooks et al, 2010; Comer et al, 2006; Krupitsky et al, 2011; Ndegwa et al, 2017; Penetar, 2012) –treatment retention rates are approximately 60% at both one month and 6 month follow-up (Kunoe et al, 2012)
• Patients with less severe dependency, using less than 6-10 bags of heroin/day show higher success in remaining opioid –free (60%), than those with more severe dependency, using 7-10 bags/day (Mogali, 2015; Sullivan et al, 2015)
• When compared with methadone, sustained-release naltrexone was associated with long-term benefits in reducing opioid-related death, while methadone maintenance was not (Ngo et al, 2008), However, methadone maintenance was associated with fewer deaths than naltrexone tablets, which must be taken daily (Gibson and Degenhardt, 2007)
• Patients treated with Vivitrol shots had fewer hospitalizations than those receiving oral medications (methadone, buprenorphine, and oral naltrexone) –the risk of an opioid-related hospitalization was 36% lower than with oral naltrexone, 63% lower than with buprenorphine, and 53% lower than with methadone; the risk for non-opioid-related hospitalization was 40%, 41%, and 58% lower than with oral naltrexone, buprenorphine, and methadone, respectively (Baser et al, 2011), Hartung et al (2014) found a 32% reduction in hospital readmissions when compared to methadone patients
• Despite higher initial costs for extended-release naltrexone, total healthcare costs over time were not significantly different than those for oral naltrexone or buprenorphine, and were 49% lower than those for methadone (Baser et al, 2011)
• When compared with methadone maintenance, naltrexone patients demonstrated improved mood and decreased depressive symptoms over time (Dean et al, 2005)
• Lower rates of re-incarceration and recidivism were associated with formerly addicted offenders released from prison on Vivitrol therapy (Gordon et al, 2015; Lee et al, 2015; Lobmaier, 2010)

RISKS

• Vivitrol induction cannot occur until 7-10 days after a patient has detoxed –wait time can be difficult for many patients, for whom relapse is high (Mannelli et al, 2011; Mogali, 2015; Ndegwa et al, 2017)
• Patients are at high risk of overdose if they discontinue treatment prematurely –opioid tolerance is lower than anticipated and they may inadvertently use a lethal amount (Gibson and Degenhardt, 2007; Kjome and Moeller, 2011; Mannelli et al, 2011; Ndegwa et al, 2017; Sigmon et al, 2012)
• Oral naltrexone, prescribed for daily use (rather than Vivitrol, administered monthly), is associated with a high rate of non-compliance –(1/4 stop treatment within days and 1/2 stop within a few weeks) (Adi et al, 2007; Kjome and Moeller, 2011; Mannelli et al, 2011; Minozzi et al, 2011; Sullivan, 2007)
• Some evidence associates naltrexone with liver damage in patients diagnosed with hepatitis (Kjome and Moeller, 2011; Ndegwa et al, 2017), and severe injection-site reactions were noted in some patients (Ndegwa et al, 2017)

Anesthesia-Assisted Rapid Opioid Detox (AAROD), also known as Ultra Rapid Opioid Detoxification (UROD), is a procedure that induces withdrawal while the patient is heavily sedated or under anesthesia. While there is no standardized procedure, the patient generally remains anesthetized for about eight or nine hours, while they are administered naltrexone, an opiate antagonist, for about four hours. The naltrexone induces severe and accelerated withdrawal. Because the patient is unconscious, they have no recollection of their withdrawal experience once they awaken –basically, the client sleeps through a very intense withdrawal.

Although some providers claim that their patients are no longer physically dependent on opioids when they awake, studies show that post-acute withdrawal symptoms, including cravings, are not eliminated, and that individuals who undergo AAROD / UROD therapy have relapse rates similar to other forms of medication-assisted treatment. For this reason, naltrexone is often prescribed to these patients once they complete the detox protocol –which typically takes two to three days.

There is a reported risk of serious adverse events, including death, with the use of anesthetics, making the risk-benefit factor an important consideration in choosing this particular detoxification method. Patients with underlying psychiatric disorders, elevated blood sugar, insulin-dependent diabetes, prior pneumonias, hepatitis, heart disease, and AIDS—are at higher risk for anesthesia-related adverse events. There is also the possibility of inadvertent overdose from the anesthetics, as well as the possibility that the individual could vomit and choke while heavily sedated. For these reasons, there has been scant support for AAROD / UROD from the medical community along with a growing consensus that the practice should be banned altogether. Opponents argue that it poses no advantage over other safer methods of detox, and the side effects associated with anesthesia make it a risky, if not dangerous option.

BENEFITS

• Quick and painless physical withdrawal –typically requiring only a two-day hospital stay (NaderiHeiden et al, 2010). Upon waking from anesthesia-induced sleep, the patient feels no greater withdrawal symptoms than patients who have undergone buprenorphine induction (Collins, et al, 2005; National Institute on Drug Abuse, 2006)
• AAROD followed by naltrexone induction is a valid treatment (Gowing et al, 2009, 2017) with a success rate of 75% at two-year follow-up according to one study (Salami et al, 2014) and 80% at nine-month follow-up according to another study (Naderi-Heiden et al, 2010), particularly for patients with high motivation, family support, and job stability (Naderi-Heiden et al, 2010)
• May be useful in detoxing methadone patients –where detox is typically prolonged and more severe than withdrawal from other opiates (Camarasa, 2007)

RISKS

• Relapse rates are similar to opiate replacement therapies –buprenorphine and methadone (Bellamy, 2015; Collins, et al, 2005; Lawental, 2000; National Institute on Drug Abuse, 2006), but relapse is potentially more deadly since the patient’s tolerance for opiates is reduced and their normal dose prior to treatment may now be lethal
• Side effects are associated with all anesthetics (inadvertent overdose, vomiting, and choking), particularly for patients with underlying somatic or psychiatric disorders (Aetna.com, 2018; Collins et al, 2005; NIDA, 2006), and these effects are potentially life-threatening (Bellamy, 2015; CDC, 2013; Cochrane Review, 2006, 2010) –however, there are less adverse effects when the patient is mildly or moderately, rather than heavily, sedated (Gowing et al, 2009, 2017; Naderi-Heiden et al, 2010)
• Round the clock medical supervision and monitoring is necessary –making this choice significantly more expensive than other treatments (Collins, et al, 2005)

By 2017, 25 states had enacted full medical marijuana (MMJ) programs, 18 states allowed limited access to MMJ products, and approximately 1.2 million medical marijuana consumers were registered in the U.S. Limited access states permit low or zero tetrahydrocannabinol (THC) and high cannabidiol (CBD) products to treat specific conditions such as uncontrolled epilepsy.

Although used as medicine in the United States until 1850 when it was added to the U.S. Pharmacopeia. According to historical documentation, physicians prescribed marijuana for a broad range of symptoms including pain, vomiting, migraine, insomnia, epilepsy, and opiate withdrawal, and it remained widely available until 1937.

Cannabis MMJ products are derived from the same plant species as recreational MJ, they are often selected for their unique cannabinoid ratios not typically sought by recreational users –high in healing properties (CBD), without the THC –the compound responsible for the “high” effect.

Although used as medicine for centuries in cultures throughout the world, MMJ did not become part of mainstream has already proven to be an effective treatment for pain, while greatly reducing the chance of dependence and eliminating risk of overdose, when compared with opioid-based medications. States with medical cannabis laws have reported a nearly 25% drop in annual opioid overdose death. MMJ patients report that cannabis is just as, or more effective than, opioid medications –alleviating pain, muscle spasms, and convulsions for multiple sclerosis and spinal cord injury patients; preventing vomiting and nausea in cancer and AIDS patients undergoing chemo and radiation therapies or antiretroviral medications; stimulating appetite in people with eating disorders; slowing chronic pain in Crohn’s Disease patients; and stopping tics associated with Tourette’s syndrome. It is reasonable to expect cannabis to have the same effects on patients suffering from opioid withdrawal –who manifest many of these exact same symptoms.

Recent studies have confirmed this hypothesis, finding that those who use cannabis during opiate withdrawal experience less severe symptoms, including significantly reduced nausea, bone pain, insomnia, and craving, while other studies have demonstrated decreased opioid dependence in lab animals. These researchers expect cannabis therapy to have a similar neurological effect on humans, and consequently open new doors for opioid detox and long-term recovery. Doctors, who are already treating opioid-dependent patients to relieve both acute and post-acute withdrawal symptoms in states where medical cannabis is legal, have documented positive results. Patients report that the majority of symptoms associated with withdrawal are reduced or eliminated, including anxiety and agitation, while sleep and digestive patterns are improved.

Other science-based findings show that marijuana ranks below caffeine on most criteria determining addiction, and may therefore be a preference for those who wish to avoid more addictive opioid maintenance therapies (methadone and buprenorphine). For individuals who reported using cannabis to wean off other more dangerous drugs (alcohol: 40%-52%; illicit drugs: 26%-33%; prescription drugs: 66%-80%), the most common reasons given for substituting cannabis were: less adverse side effects (65%), better symptom management (57%), and less withdrawal potential (34%). (Lucas et al, 2015)

Doctors, researchers, treatment providers, and consumers are slowly coming together to realize the potential of cannabis-assisted treatment as an alternative to the high-risk treatment medications currently offered to counter opioid withdrawal symptoms.

 

BENEFITS

• Reduces effects of opiate withdrawal and can potentially be used as a harm reduction strategy to reduce or replace opioid maintenance therapies without risk of overdose death (Hine et al., 1975; Morel, 2009; Dauge, 2009; Abrams, 2011; Ramesh, 2011, 2013; Scavone, 2013; Bachhuber, 2014; Bradford, 2016; Sarlin, 2016; Sulak, 2016; Boehnke, 2017; Reiman, 2009, 2017)
• Significant reductions in use of pharmaceuticals (Gruber et al, 2016; Sulak, 2016) –opiates (43%), antidepressants (18%), mood stabilizers (33%), benzodiazepines (39%), as well as sedatives and muscle relaxers (Gruber et al, 2016)
• Diminishes opiate cravings (Manwell, 2015; Reiman, 2017)
• Contributes to higher retention rates in naltrexone (Vivitrol) therapy (Raby et al, 2009)
• Improved executive functioning tasks –particularly better concentration and enhanced cognitive performance,  as well as lower impulsivity, in medical cannabis patients (Gruber et al, 2016)
• Reduction in anxiety and depression in medical cannabis patients (symptoms of post-acute opioid withdrawal), which often interfere with attention and executive function (Vytal et al, 2013; Gruber et al, 2016; Walsh, 2017)
• Lower levels of sleep disturbance and  insomnia in MMJ patients (symptoms of post-acute opioid withdrawal), which often interfere with attention and executive function (Gruber et al, 2016)
• Improved quality of life reports, particularly in increased energy and less fatigue among medical cannabis patients (Gruber et al, 2016; Sulak, 2016; Boehnke, 2017)
• Positive association between MJ use and improved cognitive performance measures –including  psychomotor speed, attention, working memory, executive functioning, and verbal learning among patients with bipolar disorder (Ringen et al, 2010; Braga et al, 2012), which has a 50%-60% predictive correlation with a co-occurring substance use disorder (Quello et al, 2005; Verduin, Tolliver and Brady, 2005)
• MMJ products which contain higher amounts of CBD and other cannabinoids may mitigate the adverse effects of recreational cannabis containing high levels of THC on cognitive performance (Englund et al, 2012, 2013; Bhattacharyya et al, 2010)

RISKS

NOTE:  A plethora of studies point to risks associated with marijuana use.  These studies mainly compare ‘marijuana use’ with ‘no drug use’.  We have not included the results of these studies, since the purpose of this compendium is to analyze potential outcomes for the efficacy of cannabis as a harm reduction model for opioid dependence.  We assume that opiate dependent brains have already been significantly compromised to render studies where the control group consists of individuals with no drug use to be insignificant to our discussion.  Also, most of these studies are concerned with recreational use, and therefore, do not make a distinction between cannabis high in CBD, a known healing compound, and cannabis high in THC, the compound used for recreational purposes to provide a ‘high’.

• 1/3 of patients experiencing acute opioid withdrawal report worsening symptoms (Herrman, 2005)

Ibogaine is a drug extracted from the root bark of the West African iboga shrub.  It has psychoactive (alterations in perception, mood, consciousness or behavior) and psychedelic (hallucinogenic) properties when ingested.

It’s effectiveness in curing opiate addiction was first discovered in 1962, by Howard Lotsof, a heroin addict living in New York.  Seeking a recreational hallucinogenic experience, he found that after a two-day intense hallucinogenic ‘trip’, he no longer felt any cravings for heroin –even more incredibly, he had no withdrawal symptoms.

Since then, studies undertaken by leading research and academic facilities have corroborated Lotsof’s experience, demonstrating that ibogaine is an effective addiction interrupter for most substances including heroin, methadone, methamphetamine, cocaine, alcohol, and nicotine. With just one dose of the hallucinogen and a psychedelic journey that can last days, heroin addicts, alcoholics and cocaine users have reportedly found themselves completely free from their cravings –with none of the usual withdrawal symptoms.

Although how it works in the brain is still not entirely clear, researchers believe that once ingested, ibogaine is converted to a metabolite, called noribogaine. This substance impacts different parts of the brain involved in drug-taking patterns of behavior –neurotransmitter pathways strongly linked to addiction and reward.  Noribogaine ‘rewires’ these areas, basically rebalancing brain chemistry by leveling out dopamine, serotonin, endorphins, adrenaline and other neuro-chemicals –thus allowing the brain to restructure itself to its pre-addicted state. It is like pressing a brain reset button.  Once this process is complete, no further use of ibogaine is necessary.  Long-term relief from withdrawal symptoms probably comes from the fact that ibogaine is stored in fat tissue and slowly released into the bloodstream for up to six months.

In addition to the complete elimination of withdrawal symptoms, users report an experience of clarity and insight into repressed emotional memories, trauma, and subconscious guilt. Many describe the experience as intensely therapeutic –similar to going through years of therapy in 24 hours, with flashbacks to pivotal life-changing experiences often repressed since childhood. Afterwards, they are left with critical insights into the root of their addiction process as well as other unhealthy behavior patterns. Through unlocking past traumatic events or situations, many of which are subconscious, individuals are suddenly able to gain understanding or clarification of the causal factors that have contributed to their compulsion to use substances.

Although medical use of ibogaine is currently not legal in the United States, it is currently used to treat opiate addiction in other countries, including Canada and Mexico. While 9 of the 28 countries presently in the European Union have similar classifications as the U.S., it is unregulated (neither officially approved nor illegal) in much of the rest of the world. New Zealand, Brazil, and South Africa have classified ibogaine as a pharmaceutical substance and restrict its use to licensed medical practitioners. This has led Americans who struggle with addiction to seek out international clinics or underground providers to receive treatment.

BENEFITS

• Eliminates craving and withdrawal symptoms associated with opiate use disorder (Alper, 1999; Alper et al., 2012; Cloutier-Gill et al., 2016; Franciotti, 2013; Glick, 1991, 1999; Heink, 2017; Lotsof and Alexander, 2001; Mačiulaitis et al., 2008; Mash et al., 1995, 2000, 2001; Noller, 2016; Sheppard, 1994)
• Clinical trials have reported rates of abstinence at twelve month follow-up of between 20% (Brown & Alper, 2017), 24% (Bastiaans, 2004), 40% – 50% (Mash, 2016), and 57% (Noller, 2016).  Other studies report that participants were either abstinent from all drug use, or had stopped use of primary and secondary drugs of choice (primary opiates) (Bastiaans, 2004)
• Ibogaine is not addictive (Koenig and Hilber, 2015; Ross, 2012)
• Perceived improvement in overall health by 58% of respondents (Bastiaans, 2004)
• Significant reductions in reported depression (Mash, 2012; Noller, 2016) by 100% of respondents (Bastiaans, 2004)
• Triggers recovery patterns for other psychological issues including anxiety disorders and post-traumatic stress disorder (Anderson, 1998; Bastiaans, 2004)
• Reduced criminal behavior (Bastiaans, 2004)
• Reported improvements in family relationships and social connectivity (Brown and Alper, 2017; Noller, 2016) in 88% of respondents (Bastiaans, 2004)
• Limited potential for abuse due to nausea and vomiting (Alper et al, 2012), and its propensity for facilitating emotionally unsettling and uncomfortable memories (Donnelly, 2011)

RISKS

• If not dosed or administered correctly, it may cause cardiac arrest or seizures  (Alper et al., 2012; Breuer et al, 2015; Hoelen, 2009; Jacobson, 2017; Maas, 2006; Noller, 2016;).  A total of 27 deaths have been reported globally since Ibogaine’s use as an anti-addictive medication (Litjens, 2016) –or 1 in 300 (maps.org)
• ‘Waking dreams’ that may be unpleasant or emotionally uncomfortable (Taylor, 2017)
• Hampers muscle coordination (Taylor, 2017)
• May induce periods of nausea and vomiting (Breuer et al, 2015; Taylor, 2017)

Kratom is a tree native to Southeast Asia –particularly, Thailand, Malaysia, Myanmar, Indonesia, and Borneo, that produces a leaf used in Asian countries as a natural analgesic and treatment for opiate addiction. Kratom leaves have been traditionally used by the people of Southeast Asia for their medicinal properties. Their use as an aid for opiate withdrawal and a cure for opiate dependence was first reported by a Dutch settler in 1897.

Pharmacologically, Kratom contains over 25 alkaloids (a group of naturally occurring chemical compounds), some of which act as opioid receptor agonists –able to impact the brain’s opioid receptors and effect mood, pain levels, and anxiety. Mitragynine, the alkaloid found in Kratom that is chiefly responsible for impacting the brain’s opioid receptors has been used for methadone detox in New Zealand.

Although it has been reported to produce a mildly euphoric effect, Kratom is not an opioid and does not produce a ‘high’ like opioids. It is one of the only plants, not derived from the opium poppy, which is capable of acting on the opioid receptors in the brain to counteract pain. The pain relief produced from ingesting the Kratom leaves –in the form of chewing the leaf or mixing the dried leaf powder in drinks or food, has been compared to using other opioid analgesics, including opium, morphine, or OxyContin.

Interestingly, although Kratom has a similar action as many opioid pain medications, it is not nearly as addictive. It also has a unique characteristic in that a low to moderate dose will usually be stimulating, while a high dose is sedating. This is apparently because the active alkaloids have both stimulant and sedative effects.

Those who use Kratom to self-detox, report that they are able to switch directly from opiates to Kratom, and then gradually reduce their Kratom use without suffering the challenging effects of opioid withdrawal. They report decreased muscle pain, reduction of cravings, decreased symptoms of depression and anxiety, less fatigue and lethargy, reduction or elimination of chills, sweats, shakes, and restless legs syndrome, normal sleep patterns, elevated levels of motivation, and increased feelings of wellness and happiness. Depending on their dose, they describe their experience as either energizing or relaxing.

Proponents agree that it is far less powerful and much less addictive than the prescription opioids (methadone and buprenorphine) that are used for opioid detox or maintenance.

 

BENEFITS

• Used to substitute for methadone or buprenorphine due to its lower potential for fatality (Boyer et al, 2008; Fluyau and Revadigar, 2017; Trakulsrichai et al., 2015) and its capacity to manage opiate withdrawal symptoms (Boyer et al, 2007; Cinosi, 2015; Feng et al, 2017; Hassan, 2013; Ismail, 2017; Prozialeck, 2016; Swogger, 2015; Vicknasingam, 2010)
• Less toxic than methadone as a harm reduction measure, and less harmful than many prescription opioids as a pain reliever (Prozialeck, 2016) –is less physically dependent, and has no correlation with respiratory depression or constipation (Prozialeck, 2016; Varadi et al, 2016)
• Used as an anti-depressant to elevate mood and alleviate depression and anxiety (Cinosi, 2015; Prozialeck, 2016; Swogger, 2015)
• Reduces fatigue (Fluyau and Revadigar, 2017)
• Does not impair social functioning despite dependency (Cinosi, 2015; Singh et al, 2015)

RISKS

• Although milder than opiate withdrawal, kratom is associated with some dependence, craving and withdrawal symptoms (McWhirter and Morris, 2010; Cinosi, 2015; Singh, 2014; Suwanlert, 1975; Trakulsrichai et al, 2015; Yusoff, 2016)
• Side effects associated with short term use include dry mouth, changes in urination, nausea, vomiting, weight loss, constipation, involuntary eye movements, tremors, muscle spasms / aches, insomnia, temporary erectile dysfunction, itching, sweating, watery eyes/nose, hot flashes, fever, diarrhea, or high blood pressure.  Psychological withdrawal symptoms commonly reported are irritability, restlessness, tension, anger, sadness, nervousness, hostility, aggression, or impaired cognition (Apryani, 2010; Cinosi, 2015, 2017; Fluyau and Revadigar, 2017; Trakulsrichai et al, 2015)
• Side effects associated with chronic use include those associated with short-term use (above), plus tremors, eventual anorexia, hyperpigmentation, and hair loss. Psychological withdrawal symptoms may include psychosis, delusions, and hallucination (Cinosi, 2015; Feng et al, 2017; Singh, 2014; Suwanlert, 1975; Trakulsrichai et al, 2015)
• High doses may cause death, arrhythmia, seizures or coma in rare instances, particularly when used in conjunction with other drugs (Anwar, 2016; Cinosi, 2015; Nelsen, 2010; Fluyau and Revadigar, 2017; Karinen, 2014; Trakulsrichai, 2013), as well as liver toxicity (Drago et al, 2017; Kapp et al, 2011)