RARE DISEASE
Cocaine intoxication
Cocaine intoxication
Cocaine intoxication
Drug discovery
2
drugs
With orphan designations
Overview
Cocaine intoxication is a stimulant toxidrome characterized by sympathomimetic hyperactivity (tachycardia, hypertension, hyperthermia), CNS excitation (agitation, seizures), and sodium channel blockade effects. Severe cases may progress to life-threatening complications including myocardial infarction, stroke, aortic dissection, rhabdomyolysis, and multi-organ failure [1][3][11]. Immediate management focuses on benzodiazepines for agitation/cardiotoxicity, aggressive cooling for hyperthermia, and alpha-blockers/phentolamine for hypertensive crises while avoiding beta-blockers [3][13][16].
Categories: rare disorders due to toxic effects
Research Papers
312 drug discovery papers about Cocaine intoxication, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
312 drug discovery papers about Cocaine intoxication, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-07-11 | Anaesthetic and intensive care management of refractory hypotension in a high-risk patient with chronic cocaine use.
Chronic cocaine use is associated with complex cardiovascular changes, including catecholamine depletion and dilated cardiomyopathy, predisposing patients to peri-operative haemodynamic instability. We report a 41-year-old man with chronic cocaine use, severe left ventricular dysfunction (left ventricular ejection fraction 20%), type 2 diabetes mellitus and recent myocardial infarction who underwent emergency surgery for perforated appendicitis. After induction of anaesthesia, he developed profound hypotension refractory to fluids and ephedrine, requiring a noradrenaline infusion. The postoperative course was complicated by septic shock and acute kidney injury requiring continuous renal replacement therapy, followed by gradual stabilisation in intensive care. This case highlights that peri-operative hypotension in patients with chronic cocaine use and advanced cardiac dysfunction may reflect catecholamine depletion rather than acute intoxication. Early use of direct acting vasopressors with planned postoperative intensive care monitoring may be crucial in reducing morbidity and mortality.
2026-06-08 | Length of Stay of Emergency Department Patients with Stimulant Intoxication Receiving Intravenous Fluid.
Intravenous (IV) fluids are routinely administered empirically in the emergency department (ED) for patients presenting with stimulant intoxication (eg, cocaine, methamphetamine, synthetic marijuana), although the literature is sparse regarding the benefits and risks of this practice. Our primary objective in this study was to assess whether empiric administration of IV fluids in the ED is associated with increased discharge length of stay (LOS) among ED patients presenting for stimulant intoxication who were subsequently discharged. This single-center, retrospective cohort study included 100 patients 18-69 years of age who were discharged from the ED with a non-incidental diagnosis related to stimulant intoxication between May 29, 2020-December 31, 2023, based on International Classification of Diseases code and chart review, in addition to a triage heart rate ≥ 90 beats per minute. We excluded patients if the medical decision-making reflected a clear indication for IV fluids or the presence of pre-defined confounding diagnoses or an uncontrolled factor that would have inherently impacted discharge LOS. Our primary outcome measure was discharge LOS. A multiple linear regression model controlled for the potentially confounding secondary outcome measures of age, sex, alcohol involvement, advanced imaging, sedation, and discharge escort. A total of 100 patients were included, including 50 (50%) patients who did not receive IV fluids and 50 (50%) patients who did. Median patient age was 35 (interquartile range [IQR] 29-41) and 73% of patients were male. Patients who received IV fluids had a median LOS of 345 minutes (IQR 260-470) vs 305 minutes (IQR 205-413), with multivariable linear regression showing no statistically significant difference (β = 40.3, 95% CI, -13.6 to 94.2, R2 = 0.162). This study suggests that empiric IV fluid administration in stimulant-intoxicated ED patients was not significantly associated with discharge length of stay. Although the observed difference and confidence interval suggest the possibility of a clinically meaningful increase in discharge LOS with empiric IV fluid, these findings should be interpreted cautiously. Time is an important resource in high-volume ED settings, and this study suggest the need for judicious use of IV fluids in the absence of a clear indication.
2026-06-05 | β-Blockers for ED Presentations with Recent Cocaine Use: A Systematic Review
Abstract Background Cocaine produces cardiovascular toxicity through intense sympathetic stimulation and direct myocardial injury, generating presentations ranging from hypertension and tachycardia to coronary vasospasm, arrhythmia, and myocardial depression. β-blockers are foundational therapies in acute coronary syndromes, yet their use after cocaine exposure remains controversial due to concerns about unopposed α-adrenergic stimulation. Methods A systematic review was conducted in accordance with PRISMA guidelines. PubMed and Google Scholar (2000–2026) were searched for observational studies of adults (≥18 years) presenting to acute care with recent cocaine use that compared outcomes between β-blocker recipients and non-recipients. Eligible studies reported in-hospital mortality, myocardial infarction/troponin rise, clinically significant arrhythmia, or haemodynamic instability. Risk of bias was assessed using the Newcastle–Ottawa Scale, and certainty of evidence using GRADE. Results Four retrospective ED cohorts (n = 1,140) met inclusion criteria; 503 patients received at least one β-blocker dose. Across studies, β-blocker use was not associated with increased in-hospital mortality or malignant arrhythmias. Myocardial infarction was heterogeneous and sensitive to definition and timing. Haemodynamic data showed no hypertensive surge and modest systolic blood pressure reductions. Risk of bias was moderate, and certainty of evidence very low to low. Conclusions In typical ED presentations of recent cocaine use, β-blocker administration does not appear to increase mortality, myocardial infarction, or malignant arrhythmias, and available haemodynamic data do not support a reproducible unopposed-α response. However, mechanistic and preclinical evidence suggests potential harm in severe intoxication or myocardial depression. A selective, phenotype-guided approach is warranted, and prospective mechanistic studies are needed. Key Points Beta-blockers did not increase deaths, heart attacks, or dangerous heart rhythms in adults who came to the emergency department after recent cocaine use. Blood pressure generally decreased after beta-blocker treatment, and no consistent “unopposed alpha” reaction was seen in typical presentations. Caution is still needed in severe intoxication or cases with heart muscle weakness, but for most emergency presentations, beta-blockers appear safe when used appropriately.
2026-03-26 | Cannabidiol (CBD) does not reduce cocaine reward or self-administration in a mouse model of schizophrenia genetic susceptibility.
Cannabidiol (CBD) is a non-intoxicating Cannabis sativa plant compound with some preclinical studies reporting efficacy for the treatment of psychiatric disorders, including schizophrenia and substance abuse. Considering that there are high rates of substance use in individuals with schizophrenia, CBD may be effective in the simultaneous treatment of both disorders. However, this exciting possibility has not been investigated preclinically, and CBD has only been evaluated for substance use treatment in healthy animals. Thus, to address this question thereby focusing on cocaine as an example for substance use, we used a mouse model of genetic risk for schizophrenia, heterozygous transmembrane domain neuregulin 1 mice (Nrg1 TM HET), which importantly show addiction-like responses to cocaine and altered schizophrenia-relevant behaviours to cannabinoids. We examined the efficacy of intraperitoneal administration of selected doses of CBD in reducing cocaine-induced conditioned place preference and locomotion (at a dose of 10 mg/kg) as well as in decreasing cocaine self-administration (at a dose of 20 mg/kg) in male Nrg1 TM HET and wildtype-like controls. The effects of prior CBD administration on the cessation and relapse-like behaviour for cocaine self-administration were also determined. The selected dose of CBD reduced cocaine place preference, cocaine locomotion and cocaine self-administration in wildtype-like littermates. However, CBD was ineffective in reducing these behaviours in Nrg1 TM HET mice. Furthermore, prior CBD treatment did not affect cessation of cocaine self-administration or relapse-like behaviour in either genotype, indicating that acute CBD administration may be needed to reduce these behaviours. Together, our findings show that CBD at the dose chosen can reduce cocaine reward, locomotion and self-administration in healthy animals. Importantly, the selected CBD treatment designs may not be effective in reducing cocaine-induced mouse behaviours in the presence of schizophrenia risk mutations including mutant Nrg1 TM. These findings advocate for research evaluating CBD's efficacy in models of substance use susceptibility or other psychiatric disorders, to determine the circumstances and treatment designs under which CBD is and is not effective for substance use treatment.
2026-03-25 | Managing acute stimulant intoxication in ambulatory settings: a protocol-driven case report.
Background: Stimulant use and overdose (known as overamping) are rising across the United States, placing strain on the healthcare system. Harm reduction strategies and behavioral interventions for overamping are more effectively implemented in ambulatory settings, which also prevents costly emergency room utilization for this vulnerable population. However, clinical guidance for ambulatory overamping management is lacking.Objective: To address this gap, we developed a protocol for patient-centered ambulatory care and present two cases demonstrating its implementation.Methods: The protocol was developed by substance use disorder clinician and pharmacy experts. We incorporated evidence for the management of acute stimulant intoxication, clinical expertise, and implementation considerations in protocol development. The protocol was reviewed by a third-party pharmacist with expertise in psychosis treatment and stimulant use disorders. We describe protocol implementation and outcomes for two cases.Results: The protocol was implemented in patients that presented with signs of overamping and consented to treatment. First-line treatment was behavioral intervention, including environmental modifications to reduce external stimuli, remaining present, addressing acute needs, and verbal de-escalation. Second-line treatment was pharmacotherapy, including benzodiazepines followed by antipsychotics. Two cases are presented, both treated initially with behavioral measures and later pharmacotherapy. Long-term follow-up demonstrates continued care and management of stimulant use.Conclusion: Protocol-driven ambulatory care of overamping has the potential to provide patient-centered compassionate care that ensures patient follow-up and promotes continued treatment.
proteins
2026-06-01 | GLP-1 Receptor Agonists in Addiction: From Observational Signals to Research Priorities
Aims: Recent large registry studies report associations between GLP-1 RA use and reduced substance-related harms. We synthesize this evidence, identify critical knowledge gaps, and define research priorities needed before clinical translation. Methods: A targeted evidence synthesis was conducted across three domains: 1. Large registry studies examining outcomes in people with AUD or opioid use disorder (OUD) prescribed GLP-1 RAs. 2. Real-world cohort studies comparing overdose and hospitalisation rates between GLP-1 RA users and non-users. 3. Neuroscience literature describing GLP-1 receptor activity in reward-related brain regions. Results: Multiple observational studies show associations between GLP-1 RA use and reduced substance-related harms. In a Swedish cohort of 227,866 individuals with AUD, semaglutide was associated with reduced alcohol-related hospitalisations (Lähteenvuo 2024). US data (>500,000 OUD, >800,000 AUD patients) showed lower opioid overdose and alcohol intoxication rates among GLP-1 RA users (Qeadan 2024; Wang 2024). All current human findings are observational, but several human randomised controlled trials are now underway, including trials of semaglutide and exenatide for AUD, semaglutide for cocaine use disorder, and liraglutide for nicotine dependence. The overlap between metabolic and addiction pathways may explain these associations, as GLP-1 signaling modulates reward processing relevant to both food intake and substance use. Preclinical studies demonstrate GLP-1R-mediated reduction in substance self-administration via reward pathway modulation in VTA, NAcc, and PFC. While this provides biological plausibility, observational human data cannot establish causality, and RCT evidence is needed. Conclusion: Observational data suggest potential associations between GLP-1 RA use and reduced substance-related harms, but cannot establish causality due to confounding. Before clinical application, essential research includes: (1) completion of ongoing RCTs with addiction-specific outcomes, (2) safety and tolerability evaluation in actively substance-using populations, including assessment of nausea/vomiting risks and drug interactions with methadone, buprenorphine, and benzodiazepines, (3) adherence and implementation feasibility studies in populations with chaotic substance use, and (4) health economics modeling. Psychiatrists should monitor emerging trial results critically as this evidence base develops in the coming years.
2026-04-19 | Substrate specificity and in vivo efficacy of engineered cocaine esterases toward cocaine and its toxic metabolites.
Cocaine abuse remains a significant global public health challenge, yet no specifically approved pharmacotherapies are currently available. While enzyme-based strategies offer promise, an effective treatment must address not only cocaine but also its major active and/or toxic metabolites-benzoylecgonine, norcocaine, and cocaethylene, several of which exhibit greater toxicity than cocaine itself. Here, we report for the first time that two engineered cocaine esterases, E196-301 and BZEase2, are capable of hydrolyzing cocaine and its three toxic metabolites. By integrating molecular modeling with comprehensive in vitro kinetic analysis and in vivo efficacy studies, we demonstrate that these enzymes possess distinct yet complementary substrate selectivity: E196-301 efficiently catalyzes the hydrolysis and clearance of cocaine, norcocaine, and cocaethylene, whereas BZEase2 preferentially degrades benzoylecgonine. Both enzymes conferred significant therapeutic benefits in rodent models of acute cocaine-metabolite exposure and cocaine-alcohol co-administration, though neither alone achieved complete detoxification against cocaine and its toxic metabolites under the tested conditions. Their complementary substrate profiles suggest combining E196-301 and BZEase2 or engineering next-generation broad-spectrum hydrolases may offer a rational strategy for comprehensive detoxification across the full spectrum of cocaine-related toxins. This work establishes a critical foundation for enzyme-based therapy targeting cocaine's multifaceted toxicology.
2025-11-27 | Medial prefrontal cortex circuit dynamics involved in stage-specific addiction.
The medial prefrontal cortex (mPFC) serves as a critical hub in addiction pathology across binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation/craving stages. This review provides the roles of the mPFC in different stages of addiction, and a focus on the mPFC neurotransmitter systems, neural circuits, molecules and synaptic adaptations on the regulation of addictive behaviors. Neurotransmitter systems of dopaminergic, glutamatergic, and GABAergic imbalances are related to pathological addiction. Circuits of dynamic dysregulation in the mPFC interaction with the striatum, nucleus accumbens (NAc), ventral tegmental area (VTA), dorsal raphe nucleus (DRN), and amygdala drive stage-specific behaviors, such as the prelimbic cortex (PL)→NAc core promoting cocaine-seeking, the infralimbic cortex (IL)→NAc shell suppressing relapse. Alterations in excitation-inhibition of microcircuits pyramidal neurons, GABAergic interneurons impair top-down regulation. Synaptic plasticity induced by drugs is involved in pathological stage-specific addiction, such as persistent craving and compulsive behaviors. Targeting the mPFC circuits offers promising therapeutic strategies for addiction intervention.
2024-02-22 | Neurovascular effects of cocaine: relevance to addiction
Cocaine is a highly addictive drug, and its use is associated with adverse medical consequences such as cerebrovascular accidents that result in debilitating neurological complications. Indeed, brain imaging studies have reported severe reductions in cerebral blood flow (CBF) in cocaine misusers when compared to the brains of healthy non-drug using controls. Such CBF deficits are likely to disrupt neuro-vascular interaction and contribute to changes in brain function. This review aims to provide an overview of cocaine-induced CBF changes and its implication to brain function and to cocaine addiction, including its effects on tissue metabolism and neuronal activity. Finally, we discuss implications for future research, including targeted pharmacological interventions and neuromodulation to limit cocaine use and mitigate the negative impacts.
2022-11-01 | From a Cycle to a Period: The Potential Role of BDNF as Plasticity and Phase-Specific Biomarker in Cocaine Use Disorder.
Cocaine Use Disorder (CUD) is one of the diseases with the greatest social and health impact, due to the high cost of rehabilitation management and the high risk of dangerous behavior and relapse. This pathology frequently leads to unsuccessful attempts to interrupt the consumption, resulting in relapses and a vicious cycle of binge/intoxication, withdrawal/negative affect, and preoccupation/ anticipation (craving). The alternation of these phases in addiction was well illustrated by Koob and colleagues in the so-called "addictive cycle", which nowadays represents a landmark in the addiction field. Recently, there has been a surge of interest in the worldwide literature for biomarkers that might explain the different stages of addiction, and one of the most studied biomarkers is, without a doubt, Brain-derived Neurotrophic Factor (BDNF). In this perspective article, we discuss the potential role of BDNF as biomarker of the CUD phases described in the "Addictive Cycle", speculating about the close relationship between BDNF fluctuations and the clinical course of CUD. We also discuss BDNF's potential role as "staging" biomarker, predicting the progression of the disease. Finding valuable biomarkers of CUD severity and disease stage could shift clinicians' focus away from behavioral symptomatic treatment and toward a novel brain-based approach, allowing for the development of more effective and targeted therapeutic strategies, thus determining major benefits for CUD patients.
antibodies
2022-09-20 | Effects of a recombinant humanized anti-cocaine monoclonal antibody on the metabolism and distribution of cocaine in vitro and in mice.
The anti-cocaine monoclonal antibody, h2E2, is a candidate for treating cocaine-use disorder. h2E2 binds to and sequesters cocaine in the plasma compartment, effectively decreasing cocaine concentrations in the brains of rats and mice. Despite the binding of cocaine to h2E2, plasma cocaine concentrations decline rapidly in rodents over time, but there was a drastic decrease in the urinary elimination of cocaine in the presence of h2E2. Since cocaine is not being renally excreted, the apparent disappearance of cocaine from the plasma must be explained by either metabolism or distribution. However, binding of cocaine to h2E2 may restrict the availability of cocaine for hydrolysis by endogenous esterases. Therefore, the antibody would be expected to extend the elimination half-life of cocaine. In contrast, previous studies reported h2E2 as having no effect on the rate of cocaine clearance. It is important to examine the ultimate clearance of the cocaine to ascertain its half-life and potential for re-intoxication. Therefore, we investigated the effects of h2E2 on cocaine hydrolysis in vitro and on cocaine metabolism and disposition in vivo over a 6-h time course. The spontaneous and enzyme-mediated in vitro hydrolysis of cocaine was drastically decreased in the presence of h2E2 in vitro. Additionally, in mice, h2E2 significantly increased the distribution and elimination half-lives of cocaine relative to vehicle controls over an extended time course. Therefore, we concluded that h2E2 slowing the distribution and elimination of cocaine is the most appropriate explanation for the initial disappearance of cocaine from the plasma in vivo.
2016-08-31 | Studies towards the improvement of an anti-cocaine monoclonal antibody for treatment of acute overdose
There is currently no clinically-approved antidote for cocaine overdose. Efforts to develop a therapy via passive immunization have resulted in a human monoclonal antibody, GNCgzk, with a high affinity for cocaine (Kd = 0.18 nM). Efforts to improve the production of antibody manifolds based on this antibody are disclosed. The engineering of an HRV 3C protease cleavage site into the GNCgzk IgG has allowed for increased production of a F(ab′)2 with a 20% superior capacity to reduce mortality for cocaine overdose in mice.
2015-10-01 | Biologic Approaches to Treat Substance-Use Disorders
Biologics reduce the amount of abused drug entering the CNS. Data emerging from clinical trials with ‘first-generation’ vaccines are ‘mixed’. Novel adjuvants and hapten redesign are strategies that may improve vaccine efficacy. A nicotine vaccine incorporating these strategies is currently in clinical trials. An antimethamphetamine mAb and bioengineered esterases are in clinical development. In contrast to traditional pharmacodynamic approaches to treat substance-use disorders (SUDs), the use of biologics (vaccines, monoclonal antibodies, and genetically modified enzymes) is based on a pharmacokinetic principle: reduce the amount of (and, ideally, eliminate) abused drug entering the central nervous system (CNS). Preclinical studies indicate that biologics are effective in both facilitating abstinence and preventing relapse to abused substances ranging from nicotine to heroin. While data are still emerging, the results from multiple clinical trials can best be described as mixed. Nonetheless, these clinical studies have already provided important insights using ‘first-generation’ tools that may inform the development of effective and commercially viable biologics to treat tobacco-, cocaine-, and methamphetamine-use disorders. In contrast to traditional pharmacodynamic approaches to treat substance-use disorders (SUDs), the use of biologics (vaccines, monoclonal antibodies, and genetically modified enzymes) is based on a pharmacokinetic principle: reduce the amount of (and, ideally, eliminate) abused drug entering the central nervous system (CNS). Preclinical studies indicate that biologics are effective in both facilitating abstinence and preventing relapse to abused substances ranging from nicotine to heroin. While data are still emerging, the results from multiple clinical trials can best be described as mixed. Nonetheless, these clinical studies have already provided important insights using ‘first-generation’ tools that may inform the development of effective and commercially viable biologics to treat tobacco-, cocaine-, and methamphetamine-use disorders.
2011-11-03 | Novel pharmacotherapeutic treatments for cocaine addiction
Cocaine is a stimulant that leads to the rapid accumulation of catecholamines and serotonin in the brain due to prevention of their re-uptake into the neuron that released the neurotransmitter. Cocaine dependence is a public health concern and cause of significant morbidity and mortality worldwide. At present, there are no approved medications for the treatment of this devastating illness, and behavioral interventions have proven to be of limited use. However, there have been a number of recent trials testing promising agents including dopamine agonists, GABAergic medications and the cocaine vaccine. Here we discuss the most recent human clinical trials of potential medications for treatment of cocaine dependence, as well as pre-clinical studies for another promising agent, levo tetrahydropalmatine. Examination of these recent findings shows promise for GABAergic medications and the cocaine vaccine, as well as unique medications such as disulfiram, whose mechanism remains to be determined. Future work may also confirm specific subgroups of patients for treatment response based on clinical characteristics, biomarkers and pharmacogenetics. This review highlights the need for further, bigger studies in order to determine optimal clinical usage.
2011-05-01 | Pharmacological Treatments for Cocaine Dependence: Is There Something New?
There is no specific and approved treatment, by regulatory authorities, for cocaine dependence. Therefore, developing new medications for the treatment of this disease continues to be a research priority. Recent advances in neurobiology and brain imaging studies have suggested several promising pharmacological approaches.Literature searches were conducted for the period from January 1990 to February 2011 using PubMed, EMBASE, PsycInfo, the NIDA research monograph index and the reference list of clinicaltrials.gov, which are the main electronic sources of ongoing trials.Recent controlled clinical studies have highlighted some very promising medications, especially glutamatergic (N-Acetylcysteine, modafinil, topiramate) and GABAergic (vigabatrin) agents, agonist replacement therapy (sustained-release methylphenidate, d-amphetamine) and dopamine agents (disulfiram). Additionally, immunotherapy is a new and promising pharmacological approach.Promising pharmacological approaches have emerged for the treatment of cocaine dependence, but larger, randomized, placebo-controlled studies are needed for some medications. Preclinical studies suggest new targets of interest in cocaine dependence. The optimal therapeutic platform is the combination of pharmacotherapies with behavioral therapies.
vaccines
2025-07-14 | Anti-drug vaccines as a harm reduction strategy: potential, limitations, and translational challenges
Abstract Background Substance use disorders (SUDs) continue to impose a major global public health burden, with persistently high relapse rates and barriers to sustained recovery. While traditional harm reduction strategies—such as opioid substitution therapy, needle exchange programs, and contingency management—have improved health outcomes, additional biomedical tools are needed. Immunotherapies, including anti-drug vaccines and monoclonal antibodies (mAbs), offer a novel adjunctive approach within the broader harm reduction framework. Main body Anti-drug vaccines stimulate the production of drug-specific antibodies that bind to psychoactive substances in the bloodstream, forming complexes too large to cross the blood–brain barrier. This may reduce reinforcement and limit intoxication. mAbs, by contrast, offer passive immunity and are being investigated for rapid-onset applications, including overdose mitigation. Preclinical and early-phase clinical trials targeting nicotine, cocaine, opioids, and methamphetamine have shown encouraging pharmacological effects. However, multiple barriers have impeded translation into practice, including interindividual variability in immune responses, short-lived antibody titers requiring boosters, behavioral compensation (e.g., dose escalation), and lack of sustained clinical efficacy in large trials. In addition, real-world implementation is limited by the absence of cost-effectiveness evaluations, regulatory ambiguity, and manufacturing complexity. Ethical issues, particularly regarding informed consent in justice-involved or marginalized populations, also warrant attention. Conclusion When integrated with behavioral, pharmacological, and psychosocial interventions, anti-drug immunotherapies may enhance the effectiveness of existing harm reduction strategies. Their potential lies not in replacing current approaches but in reinforcing them. Achieving this will require further clinical research, critical evaluation of past failures, and careful navigation of ethical, regulatory, and logistical challenges.
2024-10-25 | Specific anti-toxic immunotherapy: use in medical practice and perspectives
The results of use of approaches and means of antitoxic immunotherapy in medical practice are summarized: passive transfer of various variants of antibodies specific to toxic compounds, vaccination – specific active immunization with vaccines carrying determinants of the immunochemical specificity of target toxic compounds. The practical effectiveness of the known approaches of passive transfer and vaccination is associated with the ability of specific antibodies, by binding target bioactive compounds with pronounced toxicity, to change the availability of corresponding structures in the body-targets and, in the presence of a sufficient number of specific antibodies with high binding ability to the target compounds, neutralize their toxicity. In medical practice, polyspecific heterologous antisera or the gamma globulin fraction of antisera (extremely rare monoclonal antibodies of narrow specificity) are widely used for passive transfer as antidotes in the treatment of victims in order to prevent deaths and extensive necrosis of soft tissues at the site of the bite of poisonous snakes and insects. Active immunization – vaccination with appropriate antigenic drugs should create in immunized individuals a state of humoral immunity with the corresponding characteristics of antibody formation specific to the target compound. When a target toxic compound enters an immunized organism, it is also possible to neutralize its toxicity. The most successful experience in using the principles of active immunization as a technology for specific antitoxic therapy is associated with the practice of using toxoids for toxinemic infections. Specific practical techniques used to achieve the effectiveness of possible approaches to specific antitoxic immunotherapy in the form of passive transfer of specific antibodies or their fragments are considered: to combat lethal infections in the pathogenesis of which the toxic effects of bacterial exotoxins are significant; when treating victims of snake and insect bites, exposure to poisons of marine organisms, algae and plant toxins; in the treatment of severe intoxication with certain low molecular weight toxic substances: digoxin, colchicine, tricyclic antidepressants. The most successful experiences of using the principles of active immunization as a technology for specific antitoxic therapy, based on the use of toxoids with specificity for diphtheria, tetanus, botulism, cholera, typhoid fever, dysentery, gas gangrene and other toxinemic infections, are also considered. The fairly high immunogenicity of toxoids with the possibility of activating both constitutional and adaptive immunity has become the basis for their use as macromolecular carriers of hapten analogues of narcotic substances – a promising direction in drug addiction, in the implementation of which a number of experimental molecular and combined vaccines of opiates, methamphetamine, cocaine, and nicotine. This variant of practical efforts in medicine can be regarded as a new direction of specific antitoxic immunotherapy – an option to combat drug addiction by vaccinating drug addicts.
small molecules
2026-07-11 | Anaesthetic and intensive care management of refractory hypotension in a high-risk patient with chronic cocaine use.
Chronic cocaine use is associated with complex cardiovascular changes, including catecholamine depletion and dilated cardiomyopathy, predisposing patients to peri-operative haemodynamic instability. We report a 41-year-old man with chronic cocaine use, severe left ventricular dysfunction (left ventricular ejection fraction 20%), type 2 diabetes mellitus and recent myocardial infarction who underwent emergency surgery for perforated appendicitis. After induction of anaesthesia, he developed profound hypotension refractory to fluids and ephedrine, requiring a noradrenaline infusion. The postoperative course was complicated by septic shock and acute kidney injury requiring continuous renal replacement therapy, followed by gradual stabilisation in intensive care. This case highlights that peri-operative hypotension in patients with chronic cocaine use and advanced cardiac dysfunction may reflect catecholamine depletion rather than acute intoxication. Early use of direct acting vasopressors with planned postoperative intensive care monitoring may be crucial in reducing morbidity and mortality.
2026-06-08 | Length of Stay of Emergency Department Patients with Stimulant Intoxication Receiving Intravenous Fluid.
Intravenous (IV) fluids are routinely administered empirically in the emergency department (ED) for patients presenting with stimulant intoxication (eg, cocaine, methamphetamine, synthetic marijuana), although the literature is sparse regarding the benefits and risks of this practice. Our primary objective in this study was to assess whether empiric administration of IV fluids in the ED is associated with increased discharge length of stay (LOS) among ED patients presenting for stimulant intoxication who were subsequently discharged. This single-center, retrospective cohort study included 100 patients 18-69 years of age who were discharged from the ED with a non-incidental diagnosis related to stimulant intoxication between May 29, 2020-December 31, 2023, based on International Classification of Diseases code and chart review, in addition to a triage heart rate ≥ 90 beats per minute. We excluded patients if the medical decision-making reflected a clear indication for IV fluids or the presence of pre-defined confounding diagnoses or an uncontrolled factor that would have inherently impacted discharge LOS. Our primary outcome measure was discharge LOS. A multiple linear regression model controlled for the potentially confounding secondary outcome measures of age, sex, alcohol involvement, advanced imaging, sedation, and discharge escort. A total of 100 patients were included, including 50 (50%) patients who did not receive IV fluids and 50 (50%) patients who did. Median patient age was 35 (interquartile range [IQR] 29-41) and 73% of patients were male. Patients who received IV fluids had a median LOS of 345 minutes (IQR 260-470) vs 305 minutes (IQR 205-413), with multivariable linear regression showing no statistically significant difference (β = 40.3, 95% CI, -13.6 to 94.2, R2 = 0.162). This study suggests that empiric IV fluid administration in stimulant-intoxicated ED patients was not significantly associated with discharge length of stay. Although the observed difference and confidence interval suggest the possibility of a clinically meaningful increase in discharge LOS with empiric IV fluid, these findings should be interpreted cautiously. Time is an important resource in high-volume ED settings, and this study suggest the need for judicious use of IV fluids in the absence of a clear indication.
2026-06-05 | β-Blockers for ED Presentations with Recent Cocaine Use: A Systematic Review
Abstract Background Cocaine produces cardiovascular toxicity through intense sympathetic stimulation and direct myocardial injury, generating presentations ranging from hypertension and tachycardia to coronary vasospasm, arrhythmia, and myocardial depression. β-blockers are foundational therapies in acute coronary syndromes, yet their use after cocaine exposure remains controversial due to concerns about unopposed α-adrenergic stimulation. Methods A systematic review was conducted in accordance with PRISMA guidelines. PubMed and Google Scholar (2000–2026) were searched for observational studies of adults (≥18 years) presenting to acute care with recent cocaine use that compared outcomes between β-blocker recipients and non-recipients. Eligible studies reported in-hospital mortality, myocardial infarction/troponin rise, clinically significant arrhythmia, or haemodynamic instability. Risk of bias was assessed using the Newcastle–Ottawa Scale, and certainty of evidence using GRADE. Results Four retrospective ED cohorts (n = 1,140) met inclusion criteria; 503 patients received at least one β-blocker dose. Across studies, β-blocker use was not associated with increased in-hospital mortality or malignant arrhythmias. Myocardial infarction was heterogeneous and sensitive to definition and timing. Haemodynamic data showed no hypertensive surge and modest systolic blood pressure reductions. Risk of bias was moderate, and certainty of evidence very low to low. Conclusions In typical ED presentations of recent cocaine use, β-blocker administration does not appear to increase mortality, myocardial infarction, or malignant arrhythmias, and available haemodynamic data do not support a reproducible unopposed-α response. However, mechanistic and preclinical evidence suggests potential harm in severe intoxication or myocardial depression. A selective, phenotype-guided approach is warranted, and prospective mechanistic studies are needed. Key Points Beta-blockers did not increase deaths, heart attacks, or dangerous heart rhythms in adults who came to the emergency department after recent cocaine use. Blood pressure generally decreased after beta-blocker treatment, and no consistent “unopposed alpha” reaction was seen in typical presentations. Caution is still needed in severe intoxication or cases with heart muscle weakness, but for most emergency presentations, beta-blockers appear safe when used appropriately.
2026-03-26 | Cannabidiol (CBD) does not reduce cocaine reward or self-administration in a mouse model of schizophrenia genetic susceptibility.
Cannabidiol (CBD) is a non-intoxicating Cannabis sativa plant compound with some preclinical studies reporting efficacy for the treatment of psychiatric disorders, including schizophrenia and substance abuse. Considering that there are high rates of substance use in individuals with schizophrenia, CBD may be effective in the simultaneous treatment of both disorders. However, this exciting possibility has not been investigated preclinically, and CBD has only been evaluated for substance use treatment in healthy animals. Thus, to address this question thereby focusing on cocaine as an example for substance use, we used a mouse model of genetic risk for schizophrenia, heterozygous transmembrane domain neuregulin 1 mice (Nrg1 TM HET), which importantly show addiction-like responses to cocaine and altered schizophrenia-relevant behaviours to cannabinoids. We examined the efficacy of intraperitoneal administration of selected doses of CBD in reducing cocaine-induced conditioned place preference and locomotion (at a dose of 10 mg/kg) as well as in decreasing cocaine self-administration (at a dose of 20 mg/kg) in male Nrg1 TM HET and wildtype-like controls. The effects of prior CBD administration on the cessation and relapse-like behaviour for cocaine self-administration were also determined. The selected dose of CBD reduced cocaine place preference, cocaine locomotion and cocaine self-administration in wildtype-like littermates. However, CBD was ineffective in reducing these behaviours in Nrg1 TM HET mice. Furthermore, prior CBD treatment did not affect cessation of cocaine self-administration or relapse-like behaviour in either genotype, indicating that acute CBD administration may be needed to reduce these behaviours. Together, our findings show that CBD at the dose chosen can reduce cocaine reward, locomotion and self-administration in healthy animals. Importantly, the selected CBD treatment designs may not be effective in reducing cocaine-induced mouse behaviours in the presence of schizophrenia risk mutations including mutant Nrg1 TM. These findings advocate for research evaluating CBD's efficacy in models of substance use susceptibility or other psychiatric disorders, to determine the circumstances and treatment designs under which CBD is and is not effective for substance use treatment.
2026-03-25 | Managing acute stimulant intoxication in ambulatory settings: a protocol-driven case report.
Background: Stimulant use and overdose (known as overamping) are rising across the United States, placing strain on the healthcare system. Harm reduction strategies and behavioral interventions for overamping are more effectively implemented in ambulatory settings, which also prevents costly emergency room utilization for this vulnerable population. However, clinical guidance for ambulatory overamping management is lacking.Objective: To address this gap, we developed a protocol for patient-centered ambulatory care and present two cases demonstrating its implementation.Methods: The protocol was developed by substance use disorder clinician and pharmacy experts. We incorporated evidence for the management of acute stimulant intoxication, clinical expertise, and implementation considerations in protocol development. The protocol was reviewed by a third-party pharmacist with expertise in psychosis treatment and stimulant use disorders. We describe protocol implementation and outcomes for two cases.Results: The protocol was implemented in patients that presented with signs of overamping and consented to treatment. First-line treatment was behavioral intervention, including environmental modifications to reduce external stimuli, remaining present, addressing acute needs, and verbal de-escalation. Second-line treatment was pharmacotherapy, including benzodiazepines followed by antipsychotics. Two cases are presented, both treated initially with behavioral measures and later pharmacotherapy. Long-term follow-up demonstrates continued care and management of stimulant use.Conclusion: Protocol-driven ambulatory care of overamping has the potential to provide patient-centered compassionate care that ensures patient follow-up and promotes continued treatment.
proteins
2026-06-01 | GLP-1 Receptor Agonists in Addiction: From Observational Signals to Research Priorities
Aims: Recent large registry studies report associations between GLP-1 RA use and reduced substance-related harms. We synthesize this evidence, identify critical knowledge gaps, and define research priorities needed before clinical translation. Methods: A targeted evidence synthesis was conducted across three domains: 1. Large registry studies examining outcomes in people with AUD or opioid use disorder (OUD) prescribed GLP-1 RAs. 2. Real-world cohort studies comparing overdose and hospitalisation rates between GLP-1 RA users and non-users. 3. Neuroscience literature describing GLP-1 receptor activity in reward-related brain regions. Results: Multiple observational studies show associations between GLP-1 RA use and reduced substance-related harms. In a Swedish cohort of 227,866 individuals with AUD, semaglutide was associated with reduced alcohol-related hospitalisations (Lähteenvuo 2024). US data (>500,000 OUD, >800,000 AUD patients) showed lower opioid overdose and alcohol intoxication rates among GLP-1 RA users (Qeadan 2024; Wang 2024). All current human findings are observational, but several human randomised controlled trials are now underway, including trials of semaglutide and exenatide for AUD, semaglutide for cocaine use disorder, and liraglutide for nicotine dependence. The overlap between metabolic and addiction pathways may explain these associations, as GLP-1 signaling modulates reward processing relevant to both food intake and substance use. Preclinical studies demonstrate GLP-1R-mediated reduction in substance self-administration via reward pathway modulation in VTA, NAcc, and PFC. While this provides biological plausibility, observational human data cannot establish causality, and RCT evidence is needed. Conclusion: Observational data suggest potential associations between GLP-1 RA use and reduced substance-related harms, but cannot establish causality due to confounding. Before clinical application, essential research includes: (1) completion of ongoing RCTs with addiction-specific outcomes, (2) safety and tolerability evaluation in actively substance-using populations, including assessment of nausea/vomiting risks and drug interactions with methadone, buprenorphine, and benzodiazepines, (3) adherence and implementation feasibility studies in populations with chaotic substance use, and (4) health economics modeling. Psychiatrists should monitor emerging trial results critically as this evidence base develops in the coming years.
2026-04-19 | Substrate specificity and in vivo efficacy of engineered cocaine esterases toward cocaine and its toxic metabolites.
Cocaine abuse remains a significant global public health challenge, yet no specifically approved pharmacotherapies are currently available. While enzyme-based strategies offer promise, an effective treatment must address not only cocaine but also its major active and/or toxic metabolites-benzoylecgonine, norcocaine, and cocaethylene, several of which exhibit greater toxicity than cocaine itself. Here, we report for the first time that two engineered cocaine esterases, E196-301 and BZEase2, are capable of hydrolyzing cocaine and its three toxic metabolites. By integrating molecular modeling with comprehensive in vitro kinetic analysis and in vivo efficacy studies, we demonstrate that these enzymes possess distinct yet complementary substrate selectivity: E196-301 efficiently catalyzes the hydrolysis and clearance of cocaine, norcocaine, and cocaethylene, whereas BZEase2 preferentially degrades benzoylecgonine. Both enzymes conferred significant therapeutic benefits in rodent models of acute cocaine-metabolite exposure and cocaine-alcohol co-administration, though neither alone achieved complete detoxification against cocaine and its toxic metabolites under the tested conditions. Their complementary substrate profiles suggest combining E196-301 and BZEase2 or engineering next-generation broad-spectrum hydrolases may offer a rational strategy for comprehensive detoxification across the full spectrum of cocaine-related toxins. This work establishes a critical foundation for enzyme-based therapy targeting cocaine's multifaceted toxicology.
2025-11-27 | Medial prefrontal cortex circuit dynamics involved in stage-specific addiction.
The medial prefrontal cortex (mPFC) serves as a critical hub in addiction pathology across binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation/craving stages. This review provides the roles of the mPFC in different stages of addiction, and a focus on the mPFC neurotransmitter systems, neural circuits, molecules and synaptic adaptations on the regulation of addictive behaviors. Neurotransmitter systems of dopaminergic, glutamatergic, and GABAergic imbalances are related to pathological addiction. Circuits of dynamic dysregulation in the mPFC interaction with the striatum, nucleus accumbens (NAc), ventral tegmental area (VTA), dorsal raphe nucleus (DRN), and amygdala drive stage-specific behaviors, such as the prelimbic cortex (PL)→NAc core promoting cocaine-seeking, the infralimbic cortex (IL)→NAc shell suppressing relapse. Alterations in excitation-inhibition of microcircuits pyramidal neurons, GABAergic interneurons impair top-down regulation. Synaptic plasticity induced by drugs is involved in pathological stage-specific addiction, such as persistent craving and compulsive behaviors. Targeting the mPFC circuits offers promising therapeutic strategies for addiction intervention.
2024-02-22 | Neurovascular effects of cocaine: relevance to addiction
Cocaine is a highly addictive drug, and its use is associated with adverse medical consequences such as cerebrovascular accidents that result in debilitating neurological complications. Indeed, brain imaging studies have reported severe reductions in cerebral blood flow (CBF) in cocaine misusers when compared to the brains of healthy non-drug using controls. Such CBF deficits are likely to disrupt neuro-vascular interaction and contribute to changes in brain function. This review aims to provide an overview of cocaine-induced CBF changes and its implication to brain function and to cocaine addiction, including its effects on tissue metabolism and neuronal activity. Finally, we discuss implications for future research, including targeted pharmacological interventions and neuromodulation to limit cocaine use and mitigate the negative impacts.
2022-11-01 | From a Cycle to a Period: The Potential Role of BDNF as Plasticity and Phase-Specific Biomarker in Cocaine Use Disorder.
Cocaine Use Disorder (CUD) is one of the diseases with the greatest social and health impact, due to the high cost of rehabilitation management and the high risk of dangerous behavior and relapse. This pathology frequently leads to unsuccessful attempts to interrupt the consumption, resulting in relapses and a vicious cycle of binge/intoxication, withdrawal/negative affect, and preoccupation/ anticipation (craving). The alternation of these phases in addiction was well illustrated by Koob and colleagues in the so-called "addictive cycle", which nowadays represents a landmark in the addiction field. Recently, there has been a surge of interest in the worldwide literature for biomarkers that might explain the different stages of addiction, and one of the most studied biomarkers is, without a doubt, Brain-derived Neurotrophic Factor (BDNF). In this perspective article, we discuss the potential role of BDNF as biomarker of the CUD phases described in the "Addictive Cycle", speculating about the close relationship between BDNF fluctuations and the clinical course of CUD. We also discuss BDNF's potential role as "staging" biomarker, predicting the progression of the disease. Finding valuable biomarkers of CUD severity and disease stage could shift clinicians' focus away from behavioral symptomatic treatment and toward a novel brain-based approach, allowing for the development of more effective and targeted therapeutic strategies, thus determining major benefits for CUD patients.
antibodies
2022-09-20 | Effects of a recombinant humanized anti-cocaine monoclonal antibody on the metabolism and distribution of cocaine in vitro and in mice.
The anti-cocaine monoclonal antibody, h2E2, is a candidate for treating cocaine-use disorder. h2E2 binds to and sequesters cocaine in the plasma compartment, effectively decreasing cocaine concentrations in the brains of rats and mice. Despite the binding of cocaine to h2E2, plasma cocaine concentrations decline rapidly in rodents over time, but there was a drastic decrease in the urinary elimination of cocaine in the presence of h2E2. Since cocaine is not being renally excreted, the apparent disappearance of cocaine from the plasma must be explained by either metabolism or distribution. However, binding of cocaine to h2E2 may restrict the availability of cocaine for hydrolysis by endogenous esterases. Therefore, the antibody would be expected to extend the elimination half-life of cocaine. In contrast, previous studies reported h2E2 as having no effect on the rate of cocaine clearance. It is important to examine the ultimate clearance of the cocaine to ascertain its half-life and potential for re-intoxication. Therefore, we investigated the effects of h2E2 on cocaine hydrolysis in vitro and on cocaine metabolism and disposition in vivo over a 6-h time course. The spontaneous and enzyme-mediated in vitro hydrolysis of cocaine was drastically decreased in the presence of h2E2 in vitro. Additionally, in mice, h2E2 significantly increased the distribution and elimination half-lives of cocaine relative to vehicle controls over an extended time course. Therefore, we concluded that h2E2 slowing the distribution and elimination of cocaine is the most appropriate explanation for the initial disappearance of cocaine from the plasma in vivo.
2016-08-31 | Studies towards the improvement of an anti-cocaine monoclonal antibody for treatment of acute overdose
There is currently no clinically-approved antidote for cocaine overdose. Efforts to develop a therapy via passive immunization have resulted in a human monoclonal antibody, GNCgzk, with a high affinity for cocaine (Kd = 0.18 nM). Efforts to improve the production of antibody manifolds based on this antibody are disclosed. The engineering of an HRV 3C protease cleavage site into the GNCgzk IgG has allowed for increased production of a F(ab′)2 with a 20% superior capacity to reduce mortality for cocaine overdose in mice.
2015-10-01 | Biologic Approaches to Treat Substance-Use Disorders
Biologics reduce the amount of abused drug entering the CNS. Data emerging from clinical trials with ‘first-generation’ vaccines are ‘mixed’. Novel adjuvants and hapten redesign are strategies that may improve vaccine efficacy. A nicotine vaccine incorporating these strategies is currently in clinical trials. An antimethamphetamine mAb and bioengineered esterases are in clinical development. In contrast to traditional pharmacodynamic approaches to treat substance-use disorders (SUDs), the use of biologics (vaccines, monoclonal antibodies, and genetically modified enzymes) is based on a pharmacokinetic principle: reduce the amount of (and, ideally, eliminate) abused drug entering the central nervous system (CNS). Preclinical studies indicate that biologics are effective in both facilitating abstinence and preventing relapse to abused substances ranging from nicotine to heroin. While data are still emerging, the results from multiple clinical trials can best be described as mixed. Nonetheless, these clinical studies have already provided important insights using ‘first-generation’ tools that may inform the development of effective and commercially viable biologics to treat tobacco-, cocaine-, and methamphetamine-use disorders. In contrast to traditional pharmacodynamic approaches to treat substance-use disorders (SUDs), the use of biologics (vaccines, monoclonal antibodies, and genetically modified enzymes) is based on a pharmacokinetic principle: reduce the amount of (and, ideally, eliminate) abused drug entering the central nervous system (CNS). Preclinical studies indicate that biologics are effective in both facilitating abstinence and preventing relapse to abused substances ranging from nicotine to heroin. While data are still emerging, the results from multiple clinical trials can best be described as mixed. Nonetheless, these clinical studies have already provided important insights using ‘first-generation’ tools that may inform the development of effective and commercially viable biologics to treat tobacco-, cocaine-, and methamphetamine-use disorders.
2011-11-03 | Novel pharmacotherapeutic treatments for cocaine addiction
Cocaine is a stimulant that leads to the rapid accumulation of catecholamines and serotonin in the brain due to prevention of their re-uptake into the neuron that released the neurotransmitter. Cocaine dependence is a public health concern and cause of significant morbidity and mortality worldwide. At present, there are no approved medications for the treatment of this devastating illness, and behavioral interventions have proven to be of limited use. However, there have been a number of recent trials testing promising agents including dopamine agonists, GABAergic medications and the cocaine vaccine. Here we discuss the most recent human clinical trials of potential medications for treatment of cocaine dependence, as well as pre-clinical studies for another promising agent, levo tetrahydropalmatine. Examination of these recent findings shows promise for GABAergic medications and the cocaine vaccine, as well as unique medications such as disulfiram, whose mechanism remains to be determined. Future work may also confirm specific subgroups of patients for treatment response based on clinical characteristics, biomarkers and pharmacogenetics. This review highlights the need for further, bigger studies in order to determine optimal clinical usage.
2011-05-01 | Pharmacological Treatments for Cocaine Dependence: Is There Something New?
There is no specific and approved treatment, by regulatory authorities, for cocaine dependence. Therefore, developing new medications for the treatment of this disease continues to be a research priority. Recent advances in neurobiology and brain imaging studies have suggested several promising pharmacological approaches.Literature searches were conducted for the period from January 1990 to February 2011 using PubMed, EMBASE, PsycInfo, the NIDA research monograph index and the reference list of clinicaltrials.gov, which are the main electronic sources of ongoing trials.Recent controlled clinical studies have highlighted some very promising medications, especially glutamatergic (N-Acetylcysteine, modafinil, topiramate) and GABAergic (vigabatrin) agents, agonist replacement therapy (sustained-release methylphenidate, d-amphetamine) and dopamine agents (disulfiram). Additionally, immunotherapy is a new and promising pharmacological approach.Promising pharmacological approaches have emerged for the treatment of cocaine dependence, but larger, randomized, placebo-controlled studies are needed for some medications. Preclinical studies suggest new targets of interest in cocaine dependence. The optimal therapeutic platform is the combination of pharmacotherapies with behavioral therapies.
vaccines
2025-07-14 | Anti-drug vaccines as a harm reduction strategy: potential, limitations, and translational challenges
Abstract Background Substance use disorders (SUDs) continue to impose a major global public health burden, with persistently high relapse rates and barriers to sustained recovery. While traditional harm reduction strategies—such as opioid substitution therapy, needle exchange programs, and contingency management—have improved health outcomes, additional biomedical tools are needed. Immunotherapies, including anti-drug vaccines and monoclonal antibodies (mAbs), offer a novel adjunctive approach within the broader harm reduction framework. Main body Anti-drug vaccines stimulate the production of drug-specific antibodies that bind to psychoactive substances in the bloodstream, forming complexes too large to cross the blood–brain barrier. This may reduce reinforcement and limit intoxication. mAbs, by contrast, offer passive immunity and are being investigated for rapid-onset applications, including overdose mitigation. Preclinical and early-phase clinical trials targeting nicotine, cocaine, opioids, and methamphetamine have shown encouraging pharmacological effects. However, multiple barriers have impeded translation into practice, including interindividual variability in immune responses, short-lived antibody titers requiring boosters, behavioral compensation (e.g., dose escalation), and lack of sustained clinical efficacy in large trials. In addition, real-world implementation is limited by the absence of cost-effectiveness evaluations, regulatory ambiguity, and manufacturing complexity. Ethical issues, particularly regarding informed consent in justice-involved or marginalized populations, also warrant attention. Conclusion When integrated with behavioral, pharmacological, and psychosocial interventions, anti-drug immunotherapies may enhance the effectiveness of existing harm reduction strategies. Their potential lies not in replacing current approaches but in reinforcing them. Achieving this will require further clinical research, critical evaluation of past failures, and careful navigation of ethical, regulatory, and logistical challenges.
2024-10-25 | Specific anti-toxic immunotherapy: use in medical practice and perspectives
The results of use of approaches and means of antitoxic immunotherapy in medical practice are summarized: passive transfer of various variants of antibodies specific to toxic compounds, vaccination – specific active immunization with vaccines carrying determinants of the immunochemical specificity of target toxic compounds. The practical effectiveness of the known approaches of passive transfer and vaccination is associated with the ability of specific antibodies, by binding target bioactive compounds with pronounced toxicity, to change the availability of corresponding structures in the body-targets and, in the presence of a sufficient number of specific antibodies with high binding ability to the target compounds, neutralize their toxicity. In medical practice, polyspecific heterologous antisera or the gamma globulin fraction of antisera (extremely rare monoclonal antibodies of narrow specificity) are widely used for passive transfer as antidotes in the treatment of victims in order to prevent deaths and extensive necrosis of soft tissues at the site of the bite of poisonous snakes and insects. Active immunization – vaccination with appropriate antigenic drugs should create in immunized individuals a state of humoral immunity with the corresponding characteristics of antibody formation specific to the target compound. When a target toxic compound enters an immunized organism, it is also possible to neutralize its toxicity. The most successful experience in using the principles of active immunization as a technology for specific antitoxic therapy is associated with the practice of using toxoids for toxinemic infections. Specific practical techniques used to achieve the effectiveness of possible approaches to specific antitoxic immunotherapy in the form of passive transfer of specific antibodies or their fragments are considered: to combat lethal infections in the pathogenesis of which the toxic effects of bacterial exotoxins are significant; when treating victims of snake and insect bites, exposure to poisons of marine organisms, algae and plant toxins; in the treatment of severe intoxication with certain low molecular weight toxic substances: digoxin, colchicine, tricyclic antidepressants. The most successful experiences of using the principles of active immunization as a technology for specific antitoxic therapy, based on the use of toxoids with specificity for diphtheria, tetanus, botulism, cholera, typhoid fever, dysentery, gas gangrene and other toxinemic infections, are also considered. The fairly high immunogenicity of toxoids with the possibility of activating both constitutional and adaptive immunity has become the basis for their use as macromolecular carriers of hapten analogues of narcotic substances – a promising direction in drug addiction, in the implementation of which a number of experimental molecular and combined vaccines of opiates, methamphetamine, cocaine, and nicotine. This variant of practical efforts in medicine can be regarded as a new direction of specific antitoxic immunotherapy – an option to combat drug addiction by vaccinating drug addicts.
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Drug Discovery Landscape
2 orphan drug designations for Cocaine intoxication.
2 orphan drug designations for Cocaine intoxication.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Alpha-1-acid glycoprotein | proteins | FDA | 2004-03-05 | — | Bio Products Laboratory |
Butyrylcholinesterase | proteins | FDA | 1992-03-25 | — | Shire Laboratories Inc. |
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