ADDICTIONS AND THEIR TREATMENT (II)

Dan Prelipceanu1, Elena Clinescu2

1

MD, Prof. Dr., Head of Dept. of Psychiatry, Univ.of Medicine and Pharmacy, Bucharest, Senior Consultant Psychiatrist, Prof. Dr. Al.Obregia Psychiat. Hosp., Bucharest. Tel. +0400-21 334 72 45. Contact email: prelipceanudan@yahoo.com. 2 Resident in Psychiatry at the Clinical Hospital of Psychiatry Prof. Dr. Al. Obregia, Berceni Road No. 10-12, Bucharest, Romania. Tel. +0400-740631669. e-mail: ecalinescu@yahoo.com. Received December 13, 2010, Revised March 30, 2011, Accepted April 22, 2011.

COCAINE AND OTHER STIMULANTS COCAINE Epidemiology (14): 34,2 mil. people aged over 12 years used cocaine and 7,8 mil. used crack at some time in their lives; 5,6 mil.used annual cocaine and 1,3 mil. crack; 2 mil. were on current use of cocaine; 467 thousands were on current crack use; 1 mil. new users of cocaine (2700 daily), most of them over 18 years; average age of the firste use was 20 years; Globals consumers were 13 mil. Pattern of addictive use of cocaine is variable. It is not a predominant stereotype: Continuously use (daily) or periodically (binges), when the patients has money available (1 2 days at 2 weeks); daily use for periods of months and years; Independent on social situation, sex, race; It prevails: young people (20 40 years), polysubstance abuse (2 - 3 substances, alcohol more often), men (75%); The use is increasing because of the quality of cocaine found on the street, as well as the feeling of enlarged performances and better social functioning; The most common method of using cocaine is inhalation; It may be also administrated by intravenous /subcutaneous injections, especially in mixture with heroin (speedball) often a fatal combination. Cocaine intoxication criteria (3): A. The general criteria for acute intoxication must be met; B. There must be dysfunctional behavior or perceptual abnormalities, as evidenced by at least one of the following: 1. euphoria and sensation of increased energy; 2. hypervigilence; 3. grandiose beliefs or actions; 4. abusiveness or aggression; 5. argumentativeness; 6. lability of mood;

7. repetitive stereotyped behaviors; 8. auditory, visual, or tactile illusions; 9. hallucinations, usually with intact orientation; 10. paranoid ideation; 11. interference with personal functioning; C. At least two of the following signs must be present: 1. tachycardia (sometimes bradycardia); 2. cardiac arrhytmias; 3. hypertension (sometimes hypotension); 4. sweating and chills; 5. nausea or vomiting; 6. evidence of weight loss; 7. pupillary dilatation; 8. psychomotor agitation (sometimes retardation); 9. muscular weakness; 10. chest pain; 11. convulsions. Comment: interference with personal functioning is most readily apparent from social interactions of cocaine users, which range from extreme gregariousness to social withdrawal. Maximal detection times for urine drug testing: heavy cocaine users 22 days, light cocaine users until 3 days. Diagnosis can be done considering ICD 10 criteria. The presence of some of the signs as follows (after o suposed administration) could be relevant: Bronchodilation; Uncomfortable reversion, anxiety, dysphoric mood, fatigue, which justifies the need of a heroin dose; The effect of this condition might last up to 2 hours; At high doses: hyperpyrexia, tachycardia, hypertension, stroke risk, loss of appetite, physic and psychic stimulating, stimulation , nervosity, high anxiety, insomnia; Inhalation might cause nasal lesions (inflammation, perforation), easy to find at a physical examination; Menstrual dysfunction, amenorrhea; Sometimes pharmacopsychosis symptoms similarly to the amphetaminic psychosis (with paranoid delusions); The parenteral use: hepatitis, AIDS, abscesses, infections, scars; Pulmonary route: bronchitis, asthma, neoplasm; Euphoria and increased energy, competitive feelings, exagerated sexuality; Counteracted by anxiety, paranoid ideation; If sportmen, the athletic performance may increase, as well as with the intensification of attention and capacity to resist at physical efforts; Excessive doses: tremor, convulsions, fever; The activation of sympathetic nervous system having parallel evolution with somatic manifestations: tachycardia, hypertension, myocardial infarction. Overdose and maximum toxicity of cocaine is realized by intravenous injection.

Overdose has 2 stages: a) stimulation followed by: cephalgia, nausea, convulsions; b) physiological depression with conscience loss, respiratory depression, cardiac disorders, even decompensations; No antidote; therapeutic intervention begin with ventilation, circulatory disbalance work out, gastric lavage for oral ingestion; Diazepam for convulsive crisis; Body temperature regulation (cold pack if it is necessary); Treatment of hypertension over 160 mm Hg with cerebrovascular risk.

Cocaine withdrawal state (3): A. The general criteria for withdrawal state must be met. B. There is dysphoric mood (for instance sadness or anhedonia). C. Any two of the following signs must be present: 1. letargy and fatigue; 2. psychomotor retardation or agitation; 3. craving for cocaine; 4. increased appetite; 5. insomnia or hypersomnia; 6. bizarre or unpleasant dreams. Medical complications of cocaine dependence: Cardiac toxicity: virtually it may occurs any type of disorder from the following ones. Tachycardia after several minutes from dose administration (probably and by anesthesic effect indirect stimulation of alpha receptors); Sinus bradycardia, ventricular tachycardia, which degenerated in fibrillation, asystolia; Hypertension by adrenergic stimulation, direct proportionally with the increasing of the dose; Sudden increasing of blood pressure bleeding (cerebral haemorrhage); Myocardial infarction risk, even at young people ; Diffuse disorders within vascular walls structure: narrowing of the blood vessels, increasing of the perivascular collagen and glicoprotein deposits, inflammations regardless of the administration route ; Cocaine chronic use accelerates coronarosclerosis. Neurotoxicity: Convulsive agent even after a single administration; The same ischemic phenomenon as at the cardiac system with cerebral infarctions; Decreasing of attention, concentration, new acquisitions by learning, verbal and visual memory, verbal production, visual-motor integration; Tics, mechanical persistent repetition of the words, movements, ataxia, trouble walking which can disappear after stopping the use.

Neurological complications: Chronic use and other psychostimulants are associate with neurological degeneration: numerous cerebral ischemic foci, cerebral hemorrhage, cerebral infarctions, optical neuropathy, cerebral atrophies, cognitive impairment, mood disorders, movements disorders. Psychiatric complications: - Disinhibition, attention deficit, emotional lability, impulsivity, agressivness, depressive mood, anhedonia; - Cocaine pharmacopsychosis ( delusional states, hallucinations, psychotic anxiety, no insight, quite usual with psychotrop treatment resistance). - Depressive exacerbation can be possible at cocaine users even after a single use. Dual diagnosis: cocaine dependence is comorbid with personality disorders (antisocial, borderline), panic disorder, bipolar and cyclothymic disorder ( they use cocaine as automedication). The treatment of psychiatric complications is symptomatic (anxiolytics, antidepressants, conventional and atypical antipsychotics). Sexual complications: Spontaneous orgasm; Impotence, gynecomastia even after cessation of use; Erectile dysfunction, trouble ejaculating at big doses; Dysmenorrhea, galactorrhea, amenorrhea, infertility; trouble reaching orgasm; Perinatal complications: Born children - risk for congenital malformation, perinatal mortality.

AMPHETAMINE Amphetamines half-life (about 4 hours) is longer than cocaines (one hour) and that is why acute intoxication periods (a few days) appear rarely in comparison with cocaine, with longer pauses in this succession. Amphetamine can be administered on all routes (orally, intravenously, by sniffing or through inhalation), often mixed with another psychoactive substance (lysergic acid diethylamide, ecstasy-methylenedioxymethamphetamine). The signs and symptoms of acute amphetamine intoxication are similar with those of cocaine intoxication. General effects: Psychic effects of sympathomimetic type: tachycardia, perspiration, elevated blood pressure, tachypnea, mydriasis, anorexia, headache, dry mouth. Subjective feelings: violent flash without sedation, followed by intellectual stimulation, then an uncomfortable depressive state appears. Chronic use, use of high doses: fatigue through sleep deficiency with depressive symptoms. Behavioral effects:

 Increase in alert state, strength, verbal and motor activity, self-esteem,

concentration, feelings of well-being, decrease of appetite.

On short term, use of low doses: restlessness, euphoria, dizziness,

sleeplessness, slight confusion, tremor, possibly panic, psychotic episodes, reduced fatigue, drowsiness. At high doses symptoms become more severe: Flight of ideas, feelings of increased personal value, physical abilities, excitation, excitement, fever, perspiration. Paranoid phenomenon (amphetamine-induced psychosis), confusion. Overdoses: fever, seizures, coma, cerebral haemorrhage, death. Increase in alert state, strength, verbal and motor activity, self-esteem, concentration, feelings of well-being, decrease of appetite. On short term, use of low doses: restlessness, euphoria, dizziness, sleeplessness, slight confusion, tremor, possibly panic, psychotic episodes, reduced fatigue, drowsiness. Use in pregnancy involved the following consequences for the new born child: Statural and ponderal retardation. Cardiac and soft palate malformations. Maximal detection times for urine drug testing: 2 3 days. Tolerance and dependence evolve fastly and intensely. Chronic use of amphetamine induce psychotic disorder characterized by paranoid signs (visual and auditory hallucinations), which have a resolution in a few weeks after cessation. Withdrawal symptoms are as follows: tiredness, dormition insomnia, depressive symptoms. MDMA (ecstazy)

Ecstazy (3,4 methylene dioxymethamphetamine) is an other syntetic amphetamine (XTC, E, Adam, MDM, love drug ). MDMA is a designer drug included togheter with PGP (phenciclidine) in the halucinogene drugs cathegory. Acute intoxication are similar to those of cocaine or amphetamine. MDMA can be classified as a hallucinogen due to its psychotic potential at high doses. There is an overall tendency for using this drug in disco (raves/ techno music). The stimulant effect appears in 20-60 minutes after oral ingestion of moderate doses (50-125mg) and has a duration of 2-4 hours. There is a 2-6 hours latency period before the patient returns to normal. The peak plasmatic concentration is achieved at 2 hours after oral administration, residual levels being present even after 24 hours. Behavioral effects: Increased self-esteem. Empathy, sympathy. Feelings of intimacy, aphrodisiac effect (the most wanted effect and the most rare one).

Improved sociability and relational abilities. Euphoria, increased physical strength and plenty of emotional experiences. Negative psychological effects: anxiety, paranoia, depression. Somatic secondary effects: At moderate doses (85-100mg): tachycardia, tremulousness, nausea, bruxism, perspiration. At high doses (over 100mg): acute sensibility for cold, light, colours; vomiting; sometimes hallucinations (rarely); ataxia, nystagmus. Overdose: tachycardia, elevated or lowered blood pressure, palpitations, hyperthermia, intravascular disseminated coagulation, rabdomyolisis, dehydration, renal failure, exhaustion, feelings of cold/warmth, anxious outbursts, insomnia, aggressive reactions, psychotic states (induced by extremely high doses).

Tolerance and withdrawal signs: Tolerance develops fastly, once the doses are gradually increased. Acute withdrawal appears at 2-3 days after an use with residual effects: aches, muscle rigidity, nausea, headache, lack of appetite, blurred vision, dry mouth, insomnia. Psychological effects of amphetaminelike withdrawal: depression, anxiety, fatigue, concentration difficulty. MDMA (substituted amphetamine, amphetaminelike) withdrawal is similar in symptomatology with cocaine / amphetamine withdrawal. Treatment of cocaine and other stimulants dependence: Two studies found that disulfiram significantly reduces cocaine use at patient nonalcohol dependent, especially combined with cognitive behavioral therapy. Other studies suggest that topiramate, modafinil or acupuncture reduce, on short term, cocaine use but their effectiveness and long term safety need additional systematic studies. Antipsychotics, antidepressants, dopamine agonists (amantadine, bromocriptine) and carbamazepine were used for psychiatric complications or to reduce intake of cocaine but they have no current evidence to be clinical useful in cocaine dependence, as a 2003 Cochrane review concludes (4). The same review nave concluded that psychosocial interventions (individual and group counseling, self help groups, behavioral therapy and residential treatment) have the most chances to improve outcome of cocaine and stimulants dependent people.

HALLUCINOGENS Psychedelics or hallucinogens alter consciousness and produces confusion, auditory and / or visual hallucinations, violent behavior, without sedation or delirium. The hallucinogens incude LSD (lysergic acid diethylamide), MDMA (see above), and anticholinergics (trihexyphenidyl - Artane). Dissociative anesthetics (PCP phencyclidine, ketamine) are included by some authors (4) in this category because they share some clinical characteristics with hallucinogens. Acute intoxication due to use of hallucinogens (3): A. The general criteria for acute intoxication must be met.

B. There must be dysfunctional behavior or perceptual abnormalities, as evidenced by at least one of the following: 1. anxiety and fearfulness; 2. auditory, visual, or tactile illusions or hallucinations occuring in a state of full wakefulness and alertness; 3. depersonalisation; 4. derealisation; 5. paranoid ideation; 6. ideas of reference; 7. lability of mood; 8. hyperactivity; 9. impulsive acts; 10. impaired atention; 11. interference with personal functioning; C. At least two of the following signs must be present: 1. tachycardia; 2. palpitations; 3. sweating and chills; 4. tremor; 5. burring of vision; 6. pupillary dilatation; 7. incoordination. Intoxication with anticholinergics at dependent persons can produce hallucinations, fever, dry mouth and skin, flushed face, and visual disturbance (15). Overdose is quite rare event, but can emerged the patient becomes violent. PCP overdose can lead to manic, or on the contrary stuporous or catatonic, even coma states; cardiac / respiratory arrest can occur (4). Benzodiazepines, quetiapine (50 100 mg PO) if the patient has psychotic menifestations and verbal de escalation and reassurance, talking down are efficacious interventions. Physical withdrawal is absent, only fatigue, dysphoria and craving appear after cessation of drug, quite similar with stimulants cessation. Medical complications (hyponatremia with cerebral oedema, hepatotoxicity, hypertemia, stroke) are relevant issues. Long term use of MDMA was folowed by cognitive impairment (short -, long term memory , attention impairment). Treatment: Counseling and brief advice about medical complications in out patient settings and residential treatments can be helpful. CANNABINOIDS The plants in the genus Cannabis is cultivated worldwide. The substances of abuse derivated from Cannabis are marijuana and hashish and psychoactive component is tetrahidrocannabinol (THC). Epidemiology:

Marijuana is the most widely used illicit drug worlwide. For instance 95 million Americans age 12 and over tried it at least once, and three out of every four illicit drug users reported using marijuana within the previous 30 days (16). Todays marijuana is at least twice as strong as it was in the mid-1980s. NIDA found the average levels of THC jumped from 3.5% in 1985 to over 7% in 2003 (16). Lifetime prevalence of 15 16 year olds in some european countries (17) : Czech Republic, France, UK 35%, Ireland 32%, Netherland 28%, Italy, Slovenia 25%; past month prevalence: France 22%, Czech Republic, UK 16%, Ireland 15%, Poland 7%; lifetime prevalence at the same subpopulation four years later (17): Czech Republic 23%, France 38%, UK 38%, Ireland 39%, Netherland 28%, Italy 27%, Slovenia 36%. Cannabinoids acute intoxication criteria (3): A. The general criteria for acute intoxication must be met. B. There must be dysfunctional behavior or perceptual abnormalities, including at least one of the following: 1. euphoria or disinhibition; 2. anxiety or agitation; 3. suspiciousness or paranoid ideation; 4. temporal slowing (a sense that time is passing very slowly, and / or the person is experiencing a rapid flow of ideas); 5. impaired judgment; 6. impaired attention; 7. impaired reaction time; 8. auditory, visual, or tactile illusions; 9. hallucinations with preserved orientation; 10. depersonalization; 11. interference with personal functioning. C. At least one of the following signs must be present: 1. increased appetite; 2. dry mouth; 3. conjunctival injection; 4. tachycardia. Diagnosis: A metabolite of THC can be detected in urine as follows: one use until 3 days; daily use until 10 days, up to a month after last use for heavy, chronic users. Medical complications (4): Pulmonary complications: wheezing, cough, sputum production similar to that seen in tobacco smokers. Cardiovascular complications: tachycardia, hypertension; at higher doses predominate bradycardia, orthostatic hypertension. Psychiatric complications: probably cognitive impairment for heavy users which began tu use early, before age of 17; some studies have found an association, may be a causal relationship of marijuana use with depresion, anxiety, psychosis. Treatment: While physical addiction to cannabis can be weak, psychological addiction can nonetheless still require psychotherapeutical interventions. Withdrawal from marijuana produces increases in the severity of craving, aggression, anger, irritability and sleep difficulty,

decreased appetite, and increased emotional distress that may undermine attempts to quit using the drug. There are not for the moment a proved pharmacological treatment for marijuana dependence. Rehabilitation approaches (motivationa support achived with individual, family, group psychotherapies) if the motivation from abstinence is strong enough are the only working interventions.

GLOSSARY OF TERMS RELATED TO USE OF PSYCHOACTIVE SUBSTANCES (3, 18): Acute intoxication: A reversible condition that follows recent the administration of a psychoactive substance and results in disturbances in the level of consciousness, cognition, perception, affect or behaviour. The disturbance is related to the abuse or dependence and does not apply to nicotine. Dependence syndrome: A pattern of repeated, compulsive self administration of a psychoactive substance that result in tolerance and withdrawal. Harmful use: A pattern of psychoactive substance use that is causing physical or mental damage for health. Hazardous use (at - risk use): A pattern of psychoactive substance use that increases the risk of harmful consequences for the user. Substance abuse: Persistent or sporadic non - medical use of a psychoactive substance despite significant problems caused by the use. The criteria of substance dependence are not fulfiled. Abuse is less regular than dependence (i.e., compulsive use is not present). Psychological dependence: The subjective need to use a substance or a behaviour (eg, gambling) to maintain a feeling of satisfaction or to avoid discomfort, independent of tolerance or withdrawal symptoms. The dependent people is frustrated of being without the substance or without the opportunity to perform the behaviour. Physical (physiological) dependence: A neuroadaptation state characterised by intense physical disturbances (withdrawal / abstinence syndrome), characteristic of a particular drug, that emerge when previous, repetead, continuous exposure administration to it is stoped.

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