Withdrawal from Buprenorphine/Naloxone and Maintenance with a Natural Dopaminergic Agonist: A Cautionary Note

Abstract

Background While numerous studies support the efficacy of methadone and buprenorphine for the stabilization and maintenance of opioid dependence, clinically significant opioid withdrawal symptoms occur upon tapering and cessation of dosage. Methods We present a case study of a 35 year old Caucasian female (Krissie) who was prescribed increasing dosages of prescription opioids after carpel tunnel surgery secondary to chronic pain from reflex sympathetic dystrophy and fibromyalgia. Over the next 5 years, daily dosage requirements increased to over 80 mg of Methadone and 300 ug/hr Fentanyl transdermal patches, along with combinations of 12–14 1600 mcg Actig lollipop and oral 100 mg Morphine and 30 mg oxycodone 1–2 tabs q4-6hr PRN for breakthrough pain. Total monthly prescription costs including supplemental benzodiazepines, hypnotics and stimulants exceeded $50,000. The patient was subsequently transferred to Suboxone® in 2008, and the dosage was gradually tapered until her admission for inpatient detoxification with KB220Z a natural dopaminergic agonist. We carefully documented her withdrawal symptoms when she precipitously stopped taking buprenorphine/naloxone and during follow-up while taking KB220Z daily. We also genotyped the patient using a reward gene panel including (9 genes 18 alleles): DRD 2,3,4; MOA-A; COMT; DAT1; 5HTTLLR; OPRM1; and GABRA3. Findings At 432 days post Suboxone® withdrawal the patient is being maintained on KB220Z, has been urine tested and is opioid free. Genotyping data revealed a moderate genetic risk for addiction showing a hypodopaminergic trait. This preliminary case data suggest that the daily use of KB220Z could provide a cost effective alternative substitution adjunctive modality for Suboxone®. We encourage double-blind randomized –placebo controlled studies to test the proposition that KB220Z may act as a putative natural opioid substitution maintenance adjunct.

Buprenorphine Response as a Function of Neurogenetic Polymorphic Antecedents: Can Dopamine Genes Affect Clinical Outcomes in Reward Deficiency Syndrome (RDS)?

“…However, due to significant alteration of mood and emotion, we encourage caution in long-term maintenance with these drugs, albeit, lack of any other compounds FDA approved to date. Previously, we and others have documented severe withdrawal from buprenorphine alone or in combination in human addicts [7,24]. Here we point out that since it is known that certain dopaminergic/opiate gene polymorphisms significantly influence clinical outcomes linked to buprenorphine alone or in combination with naloxone, it seems prudent to embrace genetic testing.…”

“…Moreover, our laboratory [7] found in a genetically determined hypodopaminergic trait patient at 432 days post Suboxone® withdrawal being maintained on a putative dopamine agonist KB220Z, has been urine tested and is opioid free. Genotyping data revealed a moderate genetic risk for addiction showing a hypodopaminergic trait.…”

“…In this regard we have provided some evidence that a putative dopamine agonist (KB220Z) shows long-term potential as an opioid replacement compound especially in subjects having a genetically determined hypodopaminergic trait ( e.g. RDS ) [7]. …”

Do We Really Need to Continue Pharmacotherapy for Opioid Use Disorder (OUD) Indefinitely?

“…These effects include lower immunity, hyperalgesia, prolonged QTc interval, respiratory depression and reduced levels of a number of hormones [17]. There are a number of reports of serious withdrawal symptoms in individuals using BUP [18,19]. additionally, long-term users of BUP (average 1.6 years) have difficulty experiencing pleasure and other emotions [20].…”

Urine analysis of buprenorphine/norbuprenorphine/ naloxone in drugs and driving cases

“…Buprenorphine (2S)-2-[(5R,6R,7R,14S)-9α-Cyclopropylmethyl-4,5-epoxy-6,14-ethano-3-hydroxy-6-methoxymorphinan-7-yl]-3,3-dimethylbutan-2-ol) which is a semi-synthetic opioid. It possesses partial agonist properties acting at µ-opioid receptor site, it also possesses antagonist characteristics acting mainly on the κ-opioid receptor site [1]. Its structure is derived from thebaine, and it has a structural similarity with morphine ((5α,6α)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol), but has been reported to be up to 50 times more potent, with a higher affinity for µ-opioid receptors compared with other opioids, including heroin (diacetyl morphine) [2].…”