Cannabis and Opioid PDF

Marijuana  Marijuana refers to the dried leaves, flowers, stems, and seeds from the Cannabis sativa or Cannabis indica plant. The main active ingredient of marijuana (cannabinoids) is tetrahydrocannabinol (THC). It is metabolized to THC-carboxylic acid which is detected in the urine. T...

Marijuana  Marijuana refers to the dried leaves, flowers, stems, and seeds from the Cannabis sativa or Cannabis indica plant. The main active ingredient of marijuana (cannabinoids) is tetrahydrocannabinol (THC). It is metabolized to THC-carboxylic acid which is detected in the urine. The immediate effects of smoking marijuana include a faster heartbeat and pulse rate, bloodshot eyes, and a dry mouth and throat. The drug can impair or reduce short-term memory, alter the sense of time, and reduce the ability to do things that require concentration, swift reactions, and coordination, such as driving and operating machinery. Potential for medicinal uses of cannabinoids alleviate chemotherapy-induced nausea and vomiting. lowering intraocular pressure Anti-seizure medication muscle relaxation in spastic disorders appetite stimulation relief of phantom limb pain Menstrual cramps Migraine therapy.  Dosage : Lethal dose: 30 mg/kg. One ‘‘joint’’ weighs 0.5-1 g with an average THC content of 1% to 2% (5-20 mg); hash oil contains 30% to 50% THC; hashish is 3% to 6% THC; the toxic dose is 15 mg/kg THC. Mechanism of Action: Cannabis sativa (which contains 2% to 6% tetrahydrocannabinol) affects serotonin release along with increasing catecholaminergic effect while inhibiting parasympathetic effects. Catecholaminergic neurons are those that contain either the neurotransmitters dopamine (dopaminergic system) or norepinephrine (noradrenergic system)  Signs and Symptoms of Overdose I.V. administration can cause diarrhea, nausea, vomiting, and fevers and can progress in 12 hours to cyanosis, hypotension, renal failure, thrombocytopenia, and rhabdomyolysis. Intoxication The incidence of acute adverse reactions to marijuana is quite low. In rare cases, individuals may experience acute panic, toxic delirium, or flashbacks. These generally remit spontaneously within 12-48 hours. Management may include anxiolytics or antipsychotics if behavioral symptoms are severe. Mild cannabis intoxication (10 g/month): Fatigue, impaired recall, perceptual alterations, relaxation, sense of well-being Moderate intoxication (30 g/month): Depersonalization, memory deficits, mood swings Excessive intoxication (60 g/month): Delusions, hallucinations, impaired coordination, paranoia, slurred speech.  Admission Criteria/Prognosis Any patient who has injected a cannabinoid (need to monitor for azotemia, thrombocytopenia, and rhabdomyolysis), will require admission; severe psychotic episodes or hyperthermia will require admission. Drug Interaction Attenuation of drowsiness can occur with concomitant administration of CNS depressants. pretreatment with indomethacin may cause attenuation of the euphoria with decreased cardiac effects. cocaine, atropine along with tricyclic antidepressants may cause additive increase in heart rate. disulfiram may produce hypomanic state; may cause additive increase in blood pressure when given with amphetamines.  Toxicodynamics/Kinetics Onset of action: Inhalation: 6-12 minutes; Oral: 30-120 minutes Duration of acute effect: 0.5-3 hours Absorption: Smoking: 18% to 50%; Ingestion: 5% to 20% Distribution: Vd: 10 L/kg; increases with chronic use Metabolism: Major metabolite is 11-hydroxy-tetrahydrocannabinol Protein binding: 97% to 99% Half-life: 28 hours (first-time users); 56 hours (chronic users) Elimination: Feces (30% to 35%); renal (15% to 20%)  Marijuana metabolism/testing The mean detection time for marijuana metabolites using a 100 ng/mL urinary cutoff by immunoassay is about 24 hours. Delta-9-THC plasma levels as low as 2 ng/mL (or whole blood levels of 1.1 ng/mL) are consistent with recent usage and probably impairment. Studies have demonstrated that 94% of drivers with plasma delta-9- THC levels over 25 ng/mL have failed standard roadside testing. Pilots exposed to marijuana demonstrated impaired flying skills as long as 24 hours post-exposure  General Treatment As with other substance abuse disorders, individuals should receive psychosocial rehabilitation and there should be assessment and treatment of any coexisting psychiatric disorders. Decontamination: Ingestion: Lavage oral ingestion (within 1 hour)/activated charcoal with cathartic Supportive therapy: Benzodiazepines for agitation; hypotension can be treated with Trendelenburg/crystalloid infusion; tachycardia can be treated with beta-blockers  Tolerance generally does not develop to marijuana, although heavy daily users may Marijuana experience withdrawal symptoms of insomnia, diaphoresis, dysphoria, irritability, Withdrawal tremors, and nausea. Symptoms peak at 48 hours of abstinence and persist for 96 hours. There is no recognized withdrawal regimen Case 1 A 17-year-old male is brought to the emergency department with altered behavior. He states that he went to a party last night and tried some drugs given to him by a stranger. He reports having "weird" thoughts and feelings since taking the unknown drug. He also admits to eating much more than usual and a perception of slowed time. On physical examination, his pupils are 4 mm and reactive and conjunctival injection and ataxic gait are noted. His blood pressure is 112/75 mmHg, pulse 75/min, respiratory rate 15/min, and temperature 97.6 F (36.4 C). What is the most likely cause of this patient's condition? A. Cannabinoid receptor stimulation B. Opioid receptor stimulation C. Release of stored sympathomimetics D. NMDA receptor stimulation Case2 A 27-year-old male is brought to the emergency room by his roommate for 3 hours of altered mental status. The patient was agitated and disoriented on arrival due to place and time. His blood pressure is 165/100 mmHg (high), heart rate is 125/min (high), and temperature is 39.4°C. The roommate states that the patient suffered from an ankle fracture three days ago and is taking some medications for it. Apart from that medication, the patient was suffering from depression and was being treated for it. Which of the following is the most likely cause of the patient's symptoms? Amoxapine and amphetamines Amoxapine and tramadol Amoxapine and sibutramine Amoxapine and sumatriptan Case 3 A 24-year-old man presents with a headache. Vital signs are blood pressure 180/100 mm Hg and heart rate 140 bpm. Physical examination reveals agitation, restlessness, sweating, and dilated eyes. A urine drug screen is positive for cocaine. A head CT shows no abnormal findings. Based on the patient's history and physical examination, which of the following is the best drug to manage the patient's current condition? A. Lisinopril B. Hydralazine C. Diazepam D. Phentolamine Differences between cannabis and synthetic cannabinoids toxicity Synthetic  Synthetic cannabinoids (SC) Synthetic cannabinoids were created for therapeutic and research purposes; however, despite legal efforts to limit their availability. They have become an increasingly common drug of abuse, sold under various street names such as K2, Spice, and Black Mamba. They are associated with much more morbidity and mortality than the phytocannabinoids.  Consuming synthetic cannabinoid (SC) drugs is the desire to experience ―cannabis-like effects without the danger of being detected since SCs are mostly undetectable via standard screening tests. Curiosity, availability, easy access, and low costs may constitute additional motives in younger age groups. Sinus tachycardia, hypertension, and tachypnea were significantly recorded in association with SC intake. The hypertensive effects of synthetic cannabinoids are an opposing response to what is commonly seen in cannabis.  The predominance of neurological manifestations after SC exposure: agitation, delirium, toxic psychosis, and seizures. The use of Scs products carries a greater risk for convulsions than does the use of cannabis. These effects are most likely due to SCs-induced CB1 receptor potent full agonism in the brain. CB1 receptors are expressed by presynaptic glutamatergic or GABAergic neurons and their activation leads to decreased glutamate or GABA release with reduced excitation or suppressed inhibition, respectively. SC abuse leads to hyperemesis. As a potent agonist at CB1 receptors, SCs would be expected to cause prominent vomiting in comparison to cannabis  Among SCs group patients, there was a significant increase in the period of hospital stay in comparison to shorter periods of hospital stay needed for patients in the cannabis. Acute toxic symptoms associated with their use are also reported after intake of high doses of cannabis, but agitation, seizures, hypertension, emesis, and hypokalaemia seem to be characteristic to the synthetic cannabinoids, which are high-affinity and high-efficacy agonists of the CB1 receptor. ADVERSE HEALTH EFFECTS OF CANNABINOIDS AND SCs  Summary of acute and long-term clinical side-effects of cannabinoid- based drugs. Symptoms Type of Type of drug effect Synthetic Cannabinoids Cannabis Neuro- Acute Severe psychotic symptoms including; agitation, aggression, Perceptual alterations including; hallucinations and psychiatric catatonia, paranoia, auditory and visual hallucinations, distortion of spatial perception are typical effects. Paranoia, perceptual alterations, and persistent psychosis episode aggressiveness, and prolonged psychosis were observed in vulnerable users and are dose-related. Long-term Chronic use may increase the risk for developing psychotic An increased risk of psychotic disorders in vulnerable disorders. individuals and naïve users). Affect Acute Negative mood, panic attacks, manic behavior, depression), Anxiety and panic attacks; especially in naïve users. and suicidal ideation Long-term Depression, irritability and persistent anxiety. An increased risk for developing anxiety , and mood disorders. Cognitive Acute Severe cognitive impairments including; memory alteration, Wide range of dose-related cognitive deficits including; attention difficulties, and amnesia. attention, working-memory, cognitive inhibition, and psychomotor function. Long-term Executive function deficits of working memory and attention Impairments of set-shifting, verbal learning, attention,. short-term memory and psychomotor functions. Symptoms Type of Type of drug effect Synthetic Cannabinoids Cannabis Cardiovascular Acute Tachycardia, hypertension, myocardial infraction, An increase of cardiovascular activity, increase heart rate, arrhythmias, chest pain, and palpitations. and decrease blood pressure. Long-term Prolong use may increase risk of cardiovascular disease. An increased risk of cardiovascular disease after prolong use. Neurologic Acute Dizziness, somnolence, seizures, hypertonicity, Dizziness, somnolence, and muscle tension. hyperflexion, hyperextension, sensation changes, and fasciculations. Long-term Preliminary evidence for structural and functional Structural and functional abnormalities in a range of brain central nervous system alterations. areas including the hippocampus and amygdala. Gastro- Acute Nausea, emesis, and appetite change. Hyperemesis, and increase appetite. intestinal Long-term Severe weight-loss after prolong use. Low body weight among regular users. Other Acute Acute kidney injury, abdominal pain, miosis, mydriasis, Bronchodilation , impairments of driving ability. xerostomia, hyperthermia, fatigue, rhabdomyolysis, cough, deficits of driving ability. Long-term Kidney diseases, insomnia, nightmares, dependency, An increased risk of obstructive lung disease including lung- tolerance, and withdrawal cancer , an increased risk of cancers of the oral cavity, pharynx and esophagus, cannabis addiction, tolerance, and withdrawal. opioid Definitions Opiate: One of a group of alkaloids derived as natural products from the opium poppy (Papaver somniferum), with the ability to relieve pain, induce euphoria , induce sleep and have anti-tussive (cough suppressant) and anti-diarrhoeal properties. At higher doses, opiate induce respiratory depression and coma. Examples are morphine, codeine and thebaine (morphine and codeine have analgesic properties and depressant effects, while thebaine has no direct therapeutic effect). The term excludes synthetic opioid. Opioid: A generic term applied to natural opium alkaloids, their synthetic and semi-synthetic analogues (which in some cases may have a very different chemical structure from natural opium alkaloids) and molecules (e.g. β-endorphin, enkephalins, dynorphin) synthesised in the body which interact with opioid receptors in the brain and have the ability to induce analgesia, euphoria (a sense of well-being) and, at higher doses, respiratory depression and coma. How do heroin and other opioids work? Heroin and the opioids affect a number of different areas in the human body. The primary areas of action are the brain, spinal cord and gastrointestinal tract, where the opioids bind to receptors in the nervous system and produce their actions through processes of activation or inhibition. Receptors act as a ‘key’ in controlling physiological and psychological responses such as analgesia (pain reduction), sedation, euphoria, reduced breathing (respiratory depression), drowsiness, constricted pupils and nausea. The physiological and psychological effects differ depending on the particular opioid and the type of receptor that is activated or inhibited. Toxicokinetic Opiates can be administered intravenously (IV), topically, inhaled, intramuscularly (IM), and orally. Following intravenous administration, the peak effects of the opiate are reached within 5 to 10 minutes but may take up to 90 minutes when administered orally. Following nasal inhalation, drugs Like heroin and butorphanol can reach peak levels within 10 to 15 minutes and about 30 to 45 minutes following intramuscular injection. Fentanyl which is the only available topical analgesic agent often takes 2 to 4 hours to reach peak levels.  When administered orally, the majority of opiate absorption occurs in the small intestine. When large doses of opiates are consumed, this can lead to gastric peristalsis and a delay in gastric emptying and absorption of the drug. Once in the body, opiates are broken down by the liver to inactive compounds that are excreted primarily by the kidneys. Opiates like buprenorphine and fentanyl are highly lipid soluble and tend to redistribute into the fatty tissues and thus, have a prolonged half-life. Since all opiates are broken down by the liver, they tend to have a long half-life when consumed in the presence of liver dysfunction (for example, cirrhosis). In these patients, opiate toxicity can occur rapidly even with small doses as the drug remains in the body for a long time. Signs and Symptoms of Overdose Universally, patients with an opioid overdose will be lethargic or have a depressed level of consciousness. Patients typically will also present with respiratory depression, generalized central nervous system depression, and miosis. However, all healthcare workers need to be aware that miosis is not universally present, and that there are many other causes of respiratory depression. Other features of opiate overdose include euphoria, drowsiness, change in mental status, fresh needle marks, seizures, and conjunctival injection Ataxia, constipation, erythema multiforme, hallucinations, hypocalcemia, (SIADH), urine discoloration (milky), vomiting, Apnea, coma, dry mouth, dysuria, encephalopathy, hyponatremia, hypotension, hypothermia, impotence, myocardial depression, pulmonary edema, thirst. Opioids Intoxication Most individuals with self-induced opioid intoxication do not present for treatment unless distressing physical or behavioral symptoms occur. Anoxia, coma, and death may occur unless intervention treatment is initiated. Initial measures include airway protection, vital sign monitoring, and administration of naloxone, (an opiate antagonist). Naloxone should reverse overdose symptoms within 2 minutes. Patients with good response to naloxone may require repeated dosing over the next several hours as The duration of action of naloxone generally does not exceed 4 hours. Alternatively, nalmefene (an opiate antagonist) can reverse opioid toxicity rapidly.  Withdrawal symptoms occur within 6-12 hours after ingestion of the last drug dose in opioid-dependent persons. Treatment of opioid dependence involves the management of primarily acute physical symptoms in the acute phase. For acute phase withdrawal (detoxification), the synthetic opioid methadone has been used successfully by many clinicians who treat substance abuse disorders. In patients who begin to exhibit signs and symptoms of opioid withdrawal (hypertension, tachycardia, sweating, lacrimation, rhinorrhea), methadone 1 mg orally is given as needed over the next 24 hours for a maximum of 10-40 mg over the first day of detoxification treatment. this dose can be given for an additional 2 days, then a slow daily taper initiated until the individual is to be maintained off opioid drugs.  Methadone has proven efficacy in some groups of opioid abusers As with acute phase treatment. chronic methadone treatment dosage/format must be tailored to the individual. Generally, patients must come to the clinic daily (usually morning) to receive methadone. When used successfully, methadone maintenance reduces illegal drug use and reduces the medical, legal, and societal ramifications associated with the illicit drug culture.  Mechanism of Action Binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces generalized CNS depression. L-a-acetyl methadol (LAMM) is a long-acting opioid that has been successfully used to treat chronic opioid dependence. LAMM may eliminate the need for daily clinic visits, as is required for most methadone programs.  An alternative strategy in managing long-term opioid abuse treatment is the use of opioid antagonists. Naltrexone, a long-acting (72 hours) antagonist. It blocks the euphoric effects of opioids. Theoretically, the use of naltrexone discourages persons from opioid use as it eliminates the subsequent CNS effects. Naltrexone works best with highly motivated individuals with good psychosocial support as there are no physical incentives (withdrawal symptoms) to continue taking the opioid antagonist on a long-term basis.  Other minor tranquilizers such as chlordiazepoxide orally or clorazepate (orally) can be used to treat opiate withdrawal during the first 72 hours. Ultra-rapid opioid detoxification has been used since the 1980s with varying success. Using principles of general anesthesia in combination with an opiate antagonist, followed by naltrexone maintenance therapy. Some clinicians use the nonopioid antihypertensive clonidine to treat symptoms of acute opioid withdrawal. Clonidine may be used alone or concurrently with methadone. For acute detoxification. Due to its antihypertensive properties, pulse and blood pressure must be closely monitored.  Some patients experience excessive sedation with clonidine, which may be moderated by dosage adjustments. Gastrointestinal cramps can be treated with supportive treatment. Trazodone can be given as a sleep aid. Psychosocial and psychotherapeutic treatments are essential in promoting the lifestyle changes needed to prevent relapse. Thank you