Reduce Withdrawal Symptoms Research Articles

Efficacy of intranasal naloxone compared to other administration routes in prehospital opioid overdose management and beyond: a narrative review

Drug-related deaths in Italy, especially from opioid overdoses, increased by 6% among individuals aged 15-34 from 2014 to 2018. Opioid-related deaths rose by 6.6% in the 15-24 age group and by 5.4% in the 25-34 age group during this period. There is limited data on the effectiveness of different naloxone administration routes—intranasal (IN), intramuscular (IM), and intravenous (IV)—and no established guidelines for prehospital overdose management. Timely intervention is crucial to reduce overdose mortality. This review aims to assess the effectiveness of naloxone administration methods in opioid overdoses, focusing on prehospital settings and comparing IN, IM, and IV routes. A narrative review was conducted in accordance with PRISMA guidelines. The search included terms such as “naloxone,” “opioid overdose,” “intranasal administration,” and “prehospital emergency care,” with Boolean operators to refine the scope. The study selection was guided by the PICO framework (population, intervention, comparison, outcome). Studies were assessed for quality using the Dixon-Woods tool, and inclusion/exclusion criteria were applied. Studies will be selected based on populations treated with naloxone administered via intranasal, intramuscular, or intravenous routes, focusing on comparisons between these formulations in terms of onset time and intervention effectiveness. Out of 111 studies, five met the eligibility criteria. These studies showed that intranasal naloxone achieves higher plasma concentrations than intramuscular doses but with slower absorption and longer peak times. Additionally, intramuscular naloxone results in faster respiratory recovery and requires fewer doses. Intranasal naloxone has a bioavailability of 46.8% to 50.8% compared to intravenous naloxone, with efficacy outcomes varying by administration route. The review shows that intranasal naloxone, especially at a 2 mg dose, achieves plasma levels similar to intramuscular formulations and has linear pharmacokinetics across dosages. While its bioavailability is lower (46% to 50%) compared to intravenous administration, it is a safer and more practical option for non-clinical settings. Although intramuscular and intravenous routes work faster, the slower absorption of intranasal naloxone may help reduce withdrawal symptoms, supporting gradual dosing strategies. These findings emphasize the need for further research on optimizing naloxone dosing for synthetic opioid emergencies. This review highlights intravenous naloxone as the most effective route for opioid overdose treatment, with intramuscular and intranasal routes offering practical alternatives in prehospital settings. Intranasal naloxone, despite its lower bioavailability, provides a non-invasive option suitable for lay responders. Gradual dose escalation is recommended to minimize withdrawal symptoms. The increasing prevalence of synthetic opioids underscores the need for updated clinical guidelines on naloxone dosing and administration routes.

In patients with opioid addiction: frequent acupuncture sessions may reduce withdrawal symptoms and methadone dosage.

In patients with opioid addiction: frequent acupuncture sessions may reduce withdrawal symptoms and methadone dosage.

Efficacy of simple and very brief handgrip and isometric exercises for reducing withdrawal symptoms in cigarette smokers: A pilot randomized controlled trial.

Withdrawal symptoms lead to smoking relapse and reduce the intention to quit. The present pilot RCT examined the effect of simple and very brief handgrip and isometric exercises on reducing withdrawal symptoms, measured by the strength of tobacco craving, Questionnaire of Smoking Urges-Brief (QSU-B), Mood and Physical Symptoms Scale (MPSS), and Positive and Negative Affect Schedule (PANAS). In this 2-arm, open-labeled pilot RCT, 30 current smokers who had abstained from tobacco for at least 9 hours were randomly assigned (allocation ratio 1:1) to either the intervention group that watched a 5-minute video and did 5-minute handgrip and isometric exercises (pulling and pushing) or control group that watched 10-minute healthy-diet videos. Measurements were taken before, immediately after, and 10 minutes post-intervention. Outcomes were self-reported strength of tobacco craving, QSU-B, MPSS, and PANAS scores. The effect size for group-by-time interaction was assessed using Cohen's f2 (small=0.02, medium=0.15, large=0.35). Group-by-time interactions showed that the intervention group showed larger reductions than the control group in the strength of tobacco craving (Cohen's f2=0.54, 95% CI: 0.52-0.57), QSU-B (Cohen's f2=0.77; 95% CI: 0.74-0.80), and MPSS (Cohen's f2=0.51; 95% CI: 0.46-0.56) over the three measurement points. This RCT showed that simple and brief handgrip and isometric exercises could immediately reduce withdrawal symptoms and up to 10 minutes. in https://clinicaltrials.gov/. NCT04059497.

Impact of Nicotine Replacement Therapy Sampling on Cessation-Related Processes.

Smoking prevalence remains high among low-income smokers. Understanding processes (eg, withdrawal, craving, motivation) in early smoking cessation is crucially important for designing effective interventions for this population. This is a secondary analysis of a novel, in-session sampling intervention (ie, In Vivo) as compared with standard care behavioral smoking cessation counseling (SC) among community-dwelling low-income smokers (n = 83). This analysis examined the effect of 5 in-session sampling interventions on cessation-related processes and perceived advantages or disadvantages of nicotine replacement therapy (NRT) products over time using daily diaries. The In Vivo treatment had an early positive impact in terms of decreasing withdrawal symptoms and cravings, and increasing perceived advantages to NRT, with moderate to large effect sizes. Results also showed that the treatment effectively reduced withdrawal symptoms and cravings in-session, with small-to-medium and medium-to-large effect sizes, respectively. In-session reduction of withdrawal symptoms and cravings did not occur for the SC group, with the exception of decreased withdrawal symptoms occurring during week 4. The In Vivo treatment did not impact quit goal, desire to quit, abstinence self-efficacy, perceived difficulty in quitting, motivational engagement, or perceived disadvantages to NRT. The In Vivo group reported less daily cigarette use relative to the SC group, in addition to reporting less cigarette use on days they reported greater combination NRT use. There is preliminary support for this In Vivo treatment over SC in reducing withdrawal, craving, and the number of cigarettes smoked per day, as well as promoting perceived advantages of NRT among low-income smokers.

Review on Clinical Perspective of Multiple Substance use Disorder and its Ayurvedic Management

Background: Substance use disorder (SUD) is a condition in which there is uncontrolled use of a substance despite harmful consequences. Multiple Substance Use Disorders (MSU) include two or more substances taken together or within a short time period, either intentionally or unintentionally. This may lead to problems such as health issues, disability, failure to meet work responsibilities, and difficulties at school and home. Studies have concluded that opiates, cannabis, amphetamines, hallucinogens, inhalants, and benzodiazepines are often used in combination as well. This leads to social, academic, and occupational impairment, along with possible negative health effects. Individuals who abuse one substance are more likely to use other substances as well. Among those aged 12 or older, 61.2 million people (i.e., 21.9% of the population) used illicit drugs in the past year. Objective: To highlight the Ayurvedic clinical perspective in the management of multiple SUDs. Method: In Ayurveda, SUD may be approached by adapting the management principles of madatyaya after assessing the dosha combination as per the clinical presentation. Several combinations useful for the management of the condition, including addiction and withdrawal management, are explained. Ashtanga Lavana, Ajmodarka, Sreekandasava, and Drakshadi Kwatha are some of the medicines used internally to reduce withdrawal symptoms. Panchakarma therapies, along with yoga and Satvavajaya Chikitsa, including family therapy, have a very good outcome in managing substance withdrawal, dependence, and even inpreventing relapse. Results: By adopting the Ayurvedic principles, the outcome of MSU management may be enhanced, and the relapse may also be possible to reduced with the biopsychosocial approach. Conclusion: Evidence-based clinical studies are the need of the hour so as to prove the authenticity of such a clinical perspective explained in Ayurvedic parlance.

A qualitative longitudinal study of traumatic orthopaedic injury survivors’ experiences with pain and the long-term recovery trajectory

ObjectivesTo explore trauma patients’ experiences of the long-term recovery pathway during 18 months following hospital discharge.DesignLongitudinal qualitative study.Setting and participantsThirteen trauma patients with injuries associated with pain that had been...

The use of post-cycle therapy is associated with reduced withdrawal symptoms from anabolic-androgenic steroid use: a survey of 470 men

BackgroundAnabolic–androgenic steroids (AAS) mimic the effects of testosterone and may include testosterone itself; they are used for body enhancement within the general population. AAS use has been linked with increased mortality, cardiovascular disease, mental health disorders, and infertility. AAS-induced hypogonadism can persist for an uncertain time period despite cessation, during which men may report physical and neuropsychiatric symptoms. In an attempt to mitigate these symptoms and expedite testicular recovery, many men self-administer post-cycle-therapy (PCT), typically involving human chorionic gonadotrophin (hCG) and selective oestrogen receptor modulators (SERMs), which are known to potently stimulate testicular function. However, this practice has no objective evidence of effectiveness to lessen the severity or duration of hypogonadal symptoms.MethodsAn anonymous survey of four-hundred-and-seventy men using AAS explored the symptoms they experienced when ceasing AAS use; the effect of PCT on relieving their symptoms, and their perceived role for health service support.ResultsThe majority of respondents were white, aged 18–30 years old, and working in skilled manual work. 51.7% (n = 243) reported no issues with AAS use, but 35.3% reported increased aggression. 65.1% (n = 306) of respondents had attempted AAS cessation and 95.1% of these experienced at least one symptom upon AAS cessation. Low mood, tiredness and reduced libido were reported in 72.9%, 58.5% and 57.0% of men stopping AAS use, respectively, with only 4.9% reporting no symptoms. PCT had been used by 56.5% of respondents with AAS cessation and mitigated cravings to restart AAS use, withdrawal symptoms and suicidal thoughts by 60%, 60% and 50%, respectively. The effect of stopping AAS on body composition and recovery of testosterone or fertility was a concern in 60.5% and 52.4%, respectively. Most respondents felt PCT should be prescribed under medical supervision in the community.ConclusionsOur survey suggests that the majority of men stopping AAS use are using some form of PCT. Some self-reported symptoms of AAS-induced hypogonadism such as cravings to restart AAS use reduce by 60% and suicidal thoughts reduce by 50%. These individuals are concerned about the negative effect of AAS use and cessation. This study provides crucial information for planning future research to evaluate the effects of PCT on symptoms when men stop AAS use.

Investigation of Simulated Adherence in Long-Term Buprenorphine/Naloxone Treatment Patients

Background Buprenorphine is a medication that is used to treat opioid use disorder by reducing withdrawal symptoms and cravings for opioids. Patients with poor adherence are at higher risk of relapse and overdose. Providers often test adherence through urine testing but are not aware of simulated adherence, where patients may directly add buprenorphine to the urine samples. As of now, there exists no literature on the simulated adherence practices for patients who stayed in the treatment for more than three months Methods This study is a cross-sectional analysis of simulated adherence through urine toxicology results of 3950 patients undergoing buprenorphine/naloxone treatment. Simulated adherence was measured by the ratio of norbuprenorphine and buprenorphine <0.02 in the urine sample. Descriptive statistics as well as multivariate analysis was conducted to examine the relationship between patient information and outcomes. Results Out of 3950 patients, 411 (10.4%) had a history of one or more simulated adherence. On average, patients with multiple simulated adherences had 48.1% of their tests simulated, while on the contrary, patients with a single occurrence of simulated adherence had 17.6% of their tests simulated. Weekly testing and visit number of over 15 were associated with a higher likelihood of simulated adherence. Conclusion The study demonstrates that simulated adherence is a recurring phenomenon among buprenorphine/naloxone treatment patients regardless of the duration in the treatment. Utilization of quantitative urine toxicology to identify simulated adherence will enable healthcare providers to formulate a more precise and effective treatment plan tailored to support individual patient needs.

Smoking cessation strategies: An in-depth analysis of nicotine replacement therapy and alternatives

Introduction and purpose: The primary objective of this literature review is to thoroughly investigate the topic of nicotine replacement therapy, considering the latest discoveries and detailing various forms of available nicotine substitution. Materials and methods: Literature review of PubMed and Google Scholar databases. State of Knowledge: Tobacco smoking remains one of the leading causes of premature death worldwide, accounting for millions of deaths each year. Nicotine, the addictive component of tobacco, is responsible for sustaining cigarette smoking patterns and making smoking cessation particularly challenging. Nicotine replacement therapy (NRT) is now considered one of the primary methods to help individuals quit smoking by reducing withdrawal symptoms and cravings associated with cessation. Conclusions: Over the years, extensive research has confirmed the effectiveness and safety of NRT, resulting in the development of different forms of nicotine substitution. The outcomes of using these various forms are similar and premature discontinuation by patients remains a primary reason for NRT failure. Therefore, it is crucial for each patient to select the form of NRT that meets their individual preferences. The best results are obtained by combining multiple forms of substitution simultaneously, as well as integrating them with other therapeutic methods.

Noninvasive Vagal Nerve Stimulation for Opioid Use Disorder

Background: Opioid Use Disorder (OUD) is an escalating public health problem with over 100,000 drug overdose-related deaths last year most of them related to opioid overdose, yet treatment options remain limited. Non-invasive Vagal Nerve Stimulation (nVNS) can be delivered via the ear or the neck and is a non-medication alternative to treatment of opioid withdrawal and OUD with potentially widespread applications. Methods: This paper reviews the neurobiology of opioid withdrawal and OUD and the emerging literature of nVNS for the application of OUD. Literature databases for Pubmed, Psychinfo, and Medline were queried for these topics for 1982-present. Results: Opioid withdrawal in the context of OUD is associated with activation of peripheral sympathetic and inflammatory systems as well as alterations in central brain regions including anterior cingulate, basal ganglia, and amygdala. NVNS has the potential to reduce sympathetic and inflammatory activation and counter the effects of opioid withdrawal in initial pilot studies. Preliminary studies show that it is potentially effective at acting through sympathetic pathways to reduce the effects of opioid withdrawal, in addition to reducing pain and distress. Conclusions: NVNS shows promise as a non-medication approach to OUD, both in terms of its known effect on neurobiology as well as pilot data showing a reduction in withdrawal symptoms as well as physiological manifestations of opioid withdrawal.

Ketogenic diet: a potential adjunctive treatment for substance use disorders.

Substance use disorders (SUD) can lead to serious health problems, and there is a great interest in developing new treatment methods to alleviate the impact of substance abuse. In recent years, the ketogenic diet (KD) has shown therapeutic benefits as a dietary therapy in a variety of neurological disorders. Recent studies suggest that KD can compensate for the glucose metabolism disorders caused by alcohol use disorder by increasing ketone metabolism, thereby reducing withdrawal symptoms and indicating the therapeutic potential of KD in SUD. Additionally, SUD often accompanies increased sugar intake, involving neural circuits and altered neuroplasticity similar to substance addiction, which may induce cross-sensitization and increased use of other abused substances. Reducing carbohydrate intake through KD may have a positive effect on this. Finally, SUD is often associated with mitochondrial damage, oxidative stress, inflammation, glia dysfunction, and gut microbial disorders, while KD may potentially reverse these abnormalities and serve a therapeutic role. Although there is much indirect evidence that KD has a positive effect on SUD, the small number of relevant studies and the fact that KD leads to side effects such as metabolic abnormalities, increased risk of malnutrition and gastrointestinal symptoms have led to the limitation of KD in the treatment of SUD. Here, we described the organismal disorders caused by SUD and the possible positive effects of KD, aiming to provide potential therapeutic directions for SUD.

The Effect of Very-Long-Chain n-3 Polyunsaturated Fatty Acids in the Central Nervous System and Their Potential Benefits for Treating Alcohol Use Disorder: Reviewing Pre-Clinical and Clinical Data.

Alcohol use poses a significant global health concern, leading to serious physical and socioeconomic issues worldwide. The current treatment options for problematic alcohol consumption are limited, leading to the exploration of alternative approaches, such as nutraceuticals. One promising target is very-long-chain n-3 polyunsaturated fatty acids (VLC n-3 PUFAs). This review aims to compile the most relevant pre-clinical and clinical evidence on the effect of VLC n-3 PUFAs on alcohol use disorders and related outcomes. The findings suggest that VLC n-3 PUFAs may alleviate the physiological changes induced by alcohol consumption, including neuroinflammation and neurotransmitter dysregulation. Additionally, they can reduce withdrawal symptoms, improve mood, and reduce stress level, all of which are closely associated with problematic alcohol consumption. However, more research is required to fully understand the precise mechanisms by which VLC n-3 PUFAs exert their function. Furthermore, PUFAs should not be considered a standalone solution, but as a complement to other therapeutic approaches. Although preliminary evidence supports the potential therapeutic effect of VLC n-3 PUFAs on problematic alcohol consumption, additional research is needed to validate these findings and determine the optimal use of PUFAs as part of a comprehensive approach to the treatment of alcohol use disorders.

Evidence on Buprenorphine Dose Limits: A Review.

As overdose deaths from fentanyl continue to increase, optimizing use of medications for opioid use disorder has become increasingly important. Buprenorphine is a highly effective medication for reducing the risk of overdose death, but only if a patient remains in treatment. Shared decision making between prescribers and patients is important to establish a dose that meets each patient's treatment needs. However, patients frequently face a dose limit of 16 or 24 mg/d based on dosing guidelines on the Food and Drug Administration's package label. This review discusses patient-centered goals and clinical criteria for determining dose adequacy, reviews the history of buprenorphine dose regulation in the United States, examines pharmacological and clinical research results with buprenorphine doses up to 32 mg/d, and evaluates whether diversion concerns justify maintaining a low buprenorphine dose limit. Pharmacological and clinical research results consistently demonstrate buprenorphine's dose-dependent benefits up to at least 32 mg/d, including reductions in withdrawal symptoms, craving, opioid reward, and illicit use while improving retention in care. Diverted buprenorphine is most often used to treat withdrawal symptoms and reduce illicit opioid use when legal access to it is limited. In light of established research and profound harms from fentanyl, the Food and Drug Administration's current recommendations on target dose and dose limit are outdated and causing harm. An update to the buprenorphine package label with recommended dosing up to 32 mg/d and elimination of the 16 mg/d target dose would improve treatment effectiveness and save lives.

Buprenorphine reduces somatic withdrawal in a mouse model of early-life morphine exposure

The rising prevalence of early-life opioid exposure has become a pressing public health issue in the U.S. Neonates exposed to opioids in utero are at risk of experiencing a constellation of postpartum withdrawal symptoms commonly referred to as neonatal opioid withdrawal syndrome (NOWS). Buprenorphine (BPN), a partial agonist at the mu-opioid receptor (MOR) and antagonist at the kappa-opioid receptor (KOR), is currently approved to treat opioid use disorder in adult populations. Recent research suggests that BPN may also be effective in reducing withdrawal symptoms in neonates who were exposed to opioids in utero. We sought to determine whether BPN attenuates somatic withdrawal in a mouse model of NOWS. Our findings indicate that the administration of morphine (10mg/kg, s.c.) from postnatal day (PND) 1–14 results in increased somatic symptoms upon naloxone-precipitated (1mg/kg, s.c.) withdrawal. Co-administration of BPN (0.3mg/kg, s.c.) from PND 12–14 attenuated symptoms in morphine-treated mice. On PND 15, 24h following naloxone-precipitated withdrawal, a subset of mice was examined for thermal sensitivity in the hot plate test. BPN treatment significantly increased response latency in morphine-exposed mice. Lastly, neonatal morphine exposure elevated mRNA expression of KOR, and reduced mRNA expression of corticotropin-releasing hormone (CRH) in the periaqueductal gray when measured on PND 14. Altogether, this data provides support for the therapeutic effects of acute low-dose buprenorphine treatment in a mouse model of neonatal opioid exposure and withdrawal.

Policies Affecting Pregnant Women with Substance Use Disorder

Policies Affecting Pregnant Women with Substance Use Disorder

Methadone maintenance treatment alters couplings of default mode and salience networks in individuals with heroin use disorder: A longitudinal self-controlled resting-state fMRI study.

Methadone maintenance treatment (MMT) is a common treatment for heroin use disorder (HUD). Although individuals with HUD have been reported to show impaired coupling among the salience network (SN), executive control network (ECN), and default mode network (DMN), the effects of MMT on the coupling among three large-scale networks in individuals with HUD remains unclear. Thirty-seven individuals with HUD undergoing MMT and 57 healthy controls were recruited. The longitudinal one-year follow-up study aimed to evaluate the effects of methadone on anxiety, depression, withdrawal symptoms and craving and number of relapse, and brain function (SN, DMN and bilateral ECN) in relation to heroin dependence. The changes in psychological characteristics and the coupling among large-scale networks after 1 year of MMT were analyzed. The associations between the changes in coupling among large-scale networks and psychological characteristics and the methadone dose were also examined. After 1 year of MMT, individuals with HUD showed a reduction in the withdrawal symptom score. The number of relapses was negatively correlated with the methadone dose over 1 year. The functional connectivity between the medial prefrontal cortex (mPFC) and the left middle temporal gyrus (MTG; both key nodes of the DMN) was increased, and the connectivities between the mPFC and the anterior insular and middle frontal gyrus (key nodes of the SN) were also increased. The mPFC-left MTG connectivity was negatively correlated with the withdrawal symptom score. Long-term MMT enhanced the connectivity within the DMN which might be related to reduced withdrawal symptoms, and that between the DMN and SN which might be related to increase in salience values of heroin cues in individuals with HUD. Long-term MMT may be a double-edged sword in treatment for HUD.

In Case You Haven't Heard…

The American Society of Addiction Medicine (ASAM), in its weekly emailed summary of peer‐reviewed medical articles, includes what appears to be an advertisement for the Bridge Device, a tiny electrical signaling device that goes behind the ear and is supposed to reduce withdrawal symptoms. An open‐label study (in which patients knew that they were getting a device to reduce withdrawal symptoms) found that it did (https://onlinelibrary.wiley.com/doi/10.1002/adaw.30904). We asked ASAM whether the notice on their free weekly email was a paid advertisement or an endorsement (or maybe both). They did not respond by press time.

The Impacts of Supervised Exercise Intervention on Tobacco Withdrawal Symptoms.

This study examined a supervised moderate-intensity aerobic exercise programme's effectiveness in regulating the Tobacco Withdrawal Symptoms (TWS) during temporary abstinence. This was a single group, pre and post-quasi intervention study. Thirty daily smokers participated in an 8-week supervised moderate-intensity aerobic exercise programme. We assessed the TWS, smoking urge, mood and stress-pleasure related hormonal variables after the aerobic exercise intervention. The measurements were conducted after overnight abstinence at baseline, post-intervention (at week-8) and post-detraining (at week-10). TWS components, smoking urge and mood were found to improve. For hormonal variables, cortisol and beta-endorphin except adrenaline showed insignificant changes at post-intervention and de-training. The findings suggest moderate-intensity exercise might help in reducing withdrawal symptoms and its adverse effects. Thus, exercise is an effective adjunct treatment in a smoking cessation programme.

Effect of psychic sleep on controlling withdrawal symptoms, balance and gait among alcohol dependent patients of selected hospital of Bhubaneswar and Cuttack

Background: In worldwide alcoholism is the major issues for affecting individual’s life and for socioeconomic development. Various treatment modalities have been developed for alcoholism, yoga nidra is one of them. yoga Nidra is an easy tool and very cost effective to practice for manage these symptoms. A wide range of gastrointestinal, cardiovascular, autonomic, neurological and psychological symptoms are all a part of the acute alcohol withdrawal syndrome. Objectives 1.To assess the level of alcohol dependents with demographic variables. 2. To assess the effect of psychic sleep on controlling withdrawal symptoms, balance and gait among alcohol dependent patients. 3. To find out the association between withdrawal symptoms, balance and gait among alcohol dependent patients with selected sociodemographic variables. Methods: A Quasi-Experimental research approach with purposive sampling technique was used at IMS & SUM Hospital, Bhubaneswar and SCB, Cuttack among 72 alcohol dependent patients. Psychic sleep module of 10 sessions were given to the experimental group for 10 days following the pretest. Posttest were conducted after 10 days of psychic sleep practice. Results: The results showed a substantial difference between the levels of the pretest and posttest withdrawal symptoms, balance and gait after giving psychic sleep as evidenced by Mann- Whitney U value at p= 0.000 which is extremely significant. There was a strong significant association between intensity of withdrawal symptoms and educational status and type of family and in level of balance and gait with duration of consumption of alcohol (by using SPSS Version20 software). The psychic sleep was an effective to reducing withdrawal symptoms, balance and gait. What is already Known . The severity of the alcohol dependence syndrome was observed in psychiatric co-morbidities as mood disorders which is the most common diagnosis. . In general alcohol usage is more common among college students. . The research shows that yoga nidra was effective among college students in reducing anxiety and depression. What this paper adds . The findings of the psychic sleep study show that Yoga nidra intervention was successful in lowering withdrawal symptoms in patients who were alcohol dependent. . Those patients who are consuming alcohol and are admitted to a DE addiction center can retain balance and gait with the help of psychic sleep. . Further study can be conducted with other substance abuse cases and with larger sample.

Historical Pathways for Opioid Addiction, Withdrawal with Traditional and Alternative Treatment Options with Ketamine, Cannabinoids, and Noribogaine: A Narrative Review.

Even as prescription opioid dispensing rates have begun to decrease, the use of illicit opioids such as heroin and fentanyl has increased. Thus, the end of the opioid epidemic is not in sight, and treating patients that are addicted to opioids remains of utmost importance. Currently, the primary pharmacotherapies used to treat opioid addiction over the long term are the opioid antagonist naltrexone, the partial-agonist buprenorphine, and the full agonist methadone. Naloxone is an antagonist used to rapidly reverse opioid overdose. While these treatments are well-established and used regularly, the gravity of the opioid epidemic necessitates that all possible avenues of treatment be explored. Therefore, in this narrative review, we analyze current literature regarding use of the alternative medications ketamine, noribogaine, and cannabinoids in treating patients suffering from opioid use disorder. Beyond its use as an anesthetic, ketamine has been shown to have many applications in several medical specialties. Of particular interest to the subject at hand, ketamine is promising in treating individuals addicted to opioids, alcohol, and cocaine. Therapeutically administered cannabinoids have been proposed for the treatment of multiple illnesses. These include, but are not limited to epilepsy, Parkinson's disease, multiple sclerosis, chronic pain conditions, anxiety disorders, and addiction. The cannabinoid dronabinol has been seen to have varying effects. High doses appear to reduce withdrawal symptoms but this comes at the expense of increased adverse side effects such as sedation and tachycardia. Noribogaine is a weak MOR antagonist and relatively potent KOR agonist, which may explain the clinical anti-addictive effects. More research should be done to assess the viability of these medications for the treatment of OUD and withdrawal.