National Alliance for Drug Endangered Children Webinar Florida Alliance for Drug Endangered Children National Conference November 12, 2014 Health Consequences of Using Marijuana: Effects on Infants, Children and Young Adults Ronald Holmes, MD The attitudes about marijuana are changing. Proponents argue that it is safe or at least no more dangerous than alcohol. This attitude is supported by the availability and decriminalization of medical marijuana and recreational marijuana in several States, implying that marijuana is safe to use. Opponents argue that marijuana is dangerously addictive, a gateway to abusing other substances and that the health consequences are devastating for children, teens and young adults. As with alcohol, users need to know and understand the risks and the consequences of using marijuana. Marijuana affects different people differently. The short-term and long-term response of the user is dependent upon the dose and concentration and contents of the product and the duration and frequency of use. Its psychotropic effects are influenced by the social and behavioral environment and by the genetic traits of the individual making it difficult to generalize as to how one individual may react after using marijuana. This handout includes the following: 1. Describe the marijuana plant and its active ingredients 2. Outline the immediate effects of using marijuana 3. Review the long term health effects of marijuana on the newborn, infant, child and young adult 1
Marijuana Plants The known active ingredients in marijuana are called cannabinoids. Each plant contains over 100 different cannabinoids and over 600 other chemical substances. However, the effects of only 3-4 of the canabinnoids are known: tetrahydrocannabinol (THC) and its sister compound cannabinol (CBN), tetrahydrocannabivarin (THCV) and cannabadiol (CBD). THC is the main psychoactive component. CBN also has psychoactive properties but is about 50X less potent than THC. CBD and THCV are much less psychoactive and cause more sedation. There are 2 species of marijuana plants: Cannabis sativa (higher in THC) and Cannabis indica (higher in CBD). The concentration of cannabinoids in plants varies and is influenced by whether the plant is male or female, the time of harvest and the growing conditions. The Effects of Marijuana on the Brain: Brain Maturation, Development and Addiction Human Cannabinoids Humans make trace amounts of cannabinoids that circulate throughout the body. Cannabinoids play a vital role in growth and development of the brain. They also affect appetite, pain sensation and the response to stress and the immune system. Human cannabinoids (Endocannabinoid System) are produced in miniscule amounts and are present in the body for only an instant before they are degraded. In general they have a stabilizing, calming effect on the body, but there is a dark side. Cannabinoids present in the body for too long a time or in too high a concentration have deleterious effects. Effects of THC on development and maturation of the brain After using marijuana, the concentration of THC in the body is higher than that achieved by human cannabinoids and it is present for a prolonged period of time. The results may be disastrous. The most devastating problems occur in the developing brain and in the immune system. Excessive and/or prolonged exposure to cannabinoids may result in: 1. Disrupted development of the communication system between brain cells 2. Injury or death of brain cells 3. Impaired regulation of the immune system 2
Disruption of communication between brain cells: Brain cells communicate by releasing chemicals called neurotransmitters into the space between the cells called the synapse. These chemicals allow the nerve signal to propagate to the next cell. Neurotransmitters released by one cell are taken up by receptors in the neighboring cell and stimulate that cell to act. THC affects the release of neurotransmitters: increasing the concentration of some and decreasing the concentration of others and damages some receptors resulting in impaired communication between the brain cells. Disruption of communication between brain cells effects learning, behavior, emotions, memory and intelligence. Disruption of the immune system: Excessive and/or prolonged exposure to THC may stimulate some parts of the immune system and impede the function of other parts. Importantly, the immune cells located in the brain are over- stimulated and may attack, injure or destroy otherwise normal brain cells. Addiction to marijuana: Dopamine Nearly every addictive drug, including marijuana, targets the reward system in the brain by flooding the circuit with the neurotransmitter dopamine. The brain adapts to the overwhelming surges in dopamine by ultimately producing less dopamine and by reducing the number of dopamine receptors in the reward circuit. As a result, two important adaptations occur: (1) the addict s ability to enjoy the things that previously brought pleasure is impaired because of decreased dopamine, and (2) higher and higher doses of marijuana are needed to achieve the same high (release the same amounts of dopamine) that occurred marijuana was first used. This compels the addict to increase drug consumption leading to physiologic addiction and intense cravings for the drug. Recreational marijuana Marijuana on the streets today Marijuana (THC) is used for its mildly tranquilizing, mood and perception altering effects. Marijuana on the streets today is unlike the marijuana in the 1960 s - early 2000 s. It is a much more potent and addictive drug and is cultivated to maximize its psychoactive effect. The THC content of marijuana continues to increase. In the 60 s - 80 s the THC content ranged from 2-7%. Today it is around 23-28% and in some places may be 50% or higher. Marijuana concentrate 3
(Hashish, THC oil, BHO [Butane Hash Oil]) has become very popular. Oil is used to make marijuana edibles and infusions: cookies, cakes, brownies, pies, yogurt, ice cream and chocolates. Hashish may be a greenish brown solid substance or a brownish-tan waxy substance known on the street as wax, amber, glass, shatter, and dabs. These preparations contain 75-90% THC. Wax is usually smoked in vaporizers that may look like pens or inhalers. Vaporizers may have a section that contains a scented liquid that is used to reduce the odor of marijuana thus making smoking less detectable. Dabs or wax may also be smoked by placing a small amount on a hot paperclip. As the wax vaporizes the vapors are inhaled through a straw placed above the melting dab. Marijuana joints may be laced with other drugs such as cocaine, ecstasy, methamphetamine, heroin, or embalming fluid. The street names of marijuana joints often describe what is laced in the joint, i.e.; black ice is marijuana laced with meth, white rhino is marijuana laced with cocaine, and wet sticks or sherm is marijuana laced with embalming fluid. Embalming fluid (formaldehyde) causes hallucinations and agitation and gives the user a prolonged high. Acute effects of using marijuana Stoned : The immediate physical effects of using marijuana include euphoria, rapid heart rate, increased blood pressure and rapid respirations accompanied by dry mouth and increased appetite ( the munchies ). Other changes include slowed reaction time, impaired judgment and impaired motor coordination increasing the risk of being involved in and being responsible for a vehicular accident. Acute health risks: The dangers of smoking marijuana include impaired perception and hallucinations, loss of concentration and coordination, loss of motivation, anxiety, panic attacks, paranoia and damage to the respiratory, reproductive, and immune systems. Red-eye: The eye tissues contain cannabinoid receptors and exposure to cannabinoids causes the blood vessels in the eye to dilate resulting in red eye. Users typically carry eye drops to hide the reaction. 4
Seizures: In most people, THC causes new onset of seizures. However, this is a controversial issue and the results of scientific studies are mixed: some report that smoking marijuana may precipitate seizures while others report that marijuana suppresses seizures. There may not be a clear answer to this question because of the variability of the contents and varying concentrations of cannabinoids in marijuana and the psychological differences between people. Exposure to contaminants in marijuana: Marijuana may be contaminated with pesticides, mold, bacteria, solvent residue (butane residue) and even heavy metals. There are numerous case reports of immune-compromised smokers acquiring life threatening fungal diseases. Dealers have added glass beads and sand to joints to increase the weight and boost profits. Exposure to unknown amounts of THC and dangerous or addictive chemical adulterants: Labeling of marijuana products, both inhaled and edible varieties, is notoriously inaccurate. Users cannot trust that the concentration of THC in the product is as advertised. Other illicit drugs may be added to the joint to increase the high (embalming fluid) and to hook the user on other drugs (heroin or cocaine or meth). Edibles pose a special problem in that the onset of the desired effects is longer as compared to inhaling THC, prompting the user to think he/she has not taken enough and to ingest more. The user may than suddenly become dangerously intoxicated and experience paranoia and hallucinations. In addition, although the THC concentration in the edibles may be listed, labeling may not be accurate and the THC may not be evenly dispersed throughout the product. Risks to family and friends of using marijuana: Inadvertent exposure to THC either through exposure to second hand smoke or accidental ingestion of marijuana-edibles may pose a health threat to innocent by-standers and children. Exposure to second hand smoke results in increased blood levels of THC with all the consequences of directly inhaling or ingesting marijuana. There are numerous reports in the medical literature about accidental childhood THC poisoning resulting in hospitalization, including the necessity of ICU care. (Wang GS. JAMA Pediatr 2013;167(7):630-633 and Molly C. Arch Pediatr. 2012; 19(7):729-732). Children who have a history of asthma are prone to severe asthma attacks following exposure to marijuana smoke either via inhalation or contact with contaminated clothing. Contact with marijuana buds during the drying process may also pose a significant health threat. THC in marijuana buds is volatile (forms a gas) and exposure to buds during the drying process may result in increased blood levels of marijuana. (Ross SA. J Nat Prod 1996;59(1):49-51) 5
Chronic health effects of marijuana THC and its effects on the human brain Human cannabinoids have protective effects but excessive and/or long-term exposure to cannabinoids in marijuana adversely affects the brain. During fetal life, human cannabinoids play a major role in brain development, regulating the differentiation of immature brain cells into either mature brain cells or support cells called glia cells, guiding the migration of nerve cells to specific areas of the brain and building communication (synapses) between cells. Maternal marijuana consumption during pregnancy has significant deleterious effects on the developing brain and (1) alters the structure and function of the brain, (2) alters the release/uptake of neurotransmitters resulting in impaired brain cell communication, (3) and impairs future executive function. (Fride E, J Neuroendocrinol. 2008;20:75-81) The cannabinoid system of the infant, child, teen and young adult are also affected by marijuana. Prolonged exposure is associated with anti-social behaviors, aggressiveness and anxiety/depression. Cognitive impairment, learning problems, limited or decreasing IQ, behavioral disorders, aggression, impulsive behavior, and a variety of mental health problems are also associated with the use of marijuana. Chronic exposure of the brain to cannabinoids may activate inflammatory cells within the brain resulting in brain-cell injury and/or death (Cutano et al. J Clin Invest. 2013;123(7):2816-2831). Exposure of the fetus to marijuana (prenatal exposure) Acute effects: Exposure to marijuana, including exposure to second-hand marijuana smoke, during pregnancy has been shown to increase the risk of stillbirth 2-fold. (Varner M. Ob Gyn 2014;123(1):113-125). The study documented that blood THC levels even below the 3 ng/ml threshold of intoxication are detrimental to the unborn child. Blood levels of THC above 3.5ng/ml have been repeatedly documented in adults exposed to second-hand marijuana smoke for at least 3 hours. (Rohrich J. J Anal Toxicol 2010;34(4):196-203) Long-term effects of prenatal exposure on infants and children: A recent scientific study links fetal exposure to an increased risk for aggressive behavior and attention problems as early as 18 6
months of age. (Marroun EL. Drug Alcohol Depend 2011;118(2-3):470-474). The relationship between prenatal marijuana exposure and long-term school achievement has also been examined. As a group prenatally exposed children performed below non-exposed peers on standard intelligence tests at age 6 years, showed attention problems and depression at age 10 years and performed poorly on standardized tests to measure reading, spelling and mathematics reasoning at age 14 years. (Goldschmidt L. Neurotoxicol Teratol 2012;34(1):161-167) Exposure of the newborn and infants to marijuana Breast-feeding: Current evidence indicates that cannabis use during breastfeeding adversely affects the infant s neurodevelopment and impacts neuropsychiatric, behavioral and executive functioning. The effects on learning and behavior may influence future adult productivity and outcome. Women using cannabis during lactation should be advised about what is known and encouraged to stop using. (Jaques et al, J. Perinatol 2014, doi 10.1038/jp.2013.180) Accidental intoxication in infants and children: Infants and children may be accidentally exposed to THC through exposure to second hand smoke, volatilization of THC during drying of the marijuana plant (buds) or ingestion of marijuana edibles. Medical toxicologist George Wang and his colleagues at the Rocky Mountain Poison and Drug Center recently published a study about pediatric marijuana poisonings. "We are seeing increases in exposure to marijuana in young pediatric patients, and they have more severe symptoms than we typically associate with marijuana," Wang said, and "We hadn't seen these exposures before the big boom of the medical marijuana industry. At the Children s Hospital of Colorado there were a total of 1378 patients younger than 12 years evaluated for unintentional ingestions from January 2005 to the end of 2011. Of those, there were 0 of 790 cases due to ingestion of marijuana prior to the law s change and 14 of 588 cases after the law changed on Sept. 30, 2009. (Wang et al, JAMA Pediatrics. 2013;167(7):630-633). Persistent seizures unresponsive to treatment with anti-seizure medications: There are anecdotal reports that CBD-rich marijuana, with very low concentrations of THC, may be useful in treating severe seizures in children who have not responded to conventional therapy. A recent survey of 19 families using high-content CBD marijuana to treat their epileptic children was published: 2 children were completely seizure free, 8 reported an 80% reduction in the frequency of seizures 7
and 6 reported a reduction between 25%-60%. (Porter Epilepsy Behav 2013;29:574-577) A federally funded clinical trial is underway using CBD-rich marijuana plants. Teens and adults Dental health: Using marijuana is associated with the development of periodontal dental disease. This effect occurs in people who smoke marijuana or ingest marijuana and who only use the drug occasionally. The periodontal effects are related to the effects of cannabis on the immune system. (Ashton CH. Br J Psychiatry 2001;178:101-106) High frequency users have more severe periodontal disease causing inflammation of the gums leading to loosening of the teeth from the gums and underlying bone resulting in early age lose of teeth. (Thompson et al. JAMA, 2008;299(5):525-531) Cannabis use has also been linked to several other oral and dental problems including fiery-red gingivitis, gingival overgrowth, inflammation of the uvula and benign and cancerous oral tumors. Lung disease-emphysema and spontaneous rupture of the lungs (spontaneous pneumothorax): The well known consequences of chronic marijuana smoking include chronic cough, sputum production, wheezing and acute bronchitis (Taylor et al, Addiction 2000;95:1669-1677). Spontaneous rupture of the lungs (pneumothorax) has also been reported to be the presenting symptom of emphysema of the upper portion of the lungs in otherwise healthy asymptomatic young adults who chronically smoke marijuana but not tobacco. As a matter of routine, physicians working in Emergency Rooms now inquire about previous or current use of marijuana in any young adult who develops spontaneous pneumothorax. (Beshay M et al, European Journal of Cardio-Thoracic Surgery, 2007;32:834-838) Cyclic vomiting: The cannabis hyperemesis syndrome may occur following frequent use of marijuana for several months or years. People who develop this problem have a history of regular cannabis use, severe nausea, vomiting that recurs in a cyclic pattern over months and resolution of symptoms after stopping cannabis. Associated problems include compulsively taking hot baths to relieve the symptoms, colicky abdominal pain, and no evidence of gall bladder or pancreatic problems. (Simonetto, DA et al. Mayo Clinic Proceedings 2012;87 (2): 114 9). 8
Cardiovascular problems: There are multiple reports of rapid and irregular heart beats (atrial fibrillation) in children and adults following exposure to cannabis. (Singh et al. Pediatrics 2014;133(2):e443-446, & Korantzopoulos et al, Am J Card 2014;113(6):1085-1086). Cannabis use is associated with other cardiovascular complications. A recent report from France, where reactions to substance abuse must be reported, revealed that from 2006-2010, 1.8% of all cannabis-related sequella were cardiovascular, including acute chest pain, inflammation and obstruction in small sized arteries. (Jouanjus et al, J Am Heart Assoc. 2014;3:e000638) The actual mechanisms of these effects are not fully understood but may include damage to actions blood vessel walls and the release of substances that cause blood vessels to constrict. (Stanley, Br J Pharmacol 2014;171:1361-1378) Stroke: Stroke in young people (age 15 and above) is strongly associated with smoking marijuana. Marijuana is classified as a vasoactive substance. These substances affect the wall of the artery, resulting in spasm of the artery and inflammation that can obstruct the artery. In strokes of this type, more than one artery is typically affected. (Wolff et al. Cerebrovasc Dis 2014;37:438-443) Chronic depression, schizophrenia and psychosis: Short-term psychological effects include: a distorted sense of time, magical or "random" thinking, short-term memory loss and depression. These psychological problems generally ease after a few hours but residual effects can last for days. There is a significant and consistent relationship between marijuana use and the development of schizophrenia, chronic depression and psychosis. The results of scientific studies showing an association between marijuana use and these mental disorders are alarming but the mechanism is yet unknown. A prevalence rate of persistent depression as high as 40% in chronic marijuana smokers has been reported (Brook JS. Psychol Rep 2011;108(2):339-357). Marijuana use is a "causal component" in the development of schizophrenia and other psychotic disorders. (Caspi et al. Biol Psychiatry, May 2005) The mechanism of action is not clear but studies have implicate sudden depletion of the dopamine. (Strejilevich SA et al. Med Hypotheses 2012;78(1):107-112) A number of well-designed scientific studies have shown an association between chronic marijuana use and increased rates of chronic depression and schizophrenia in people with abnormalities of the COMT gene. Variations in the COMT gene are present in 1:4000 live births (Zammit et al. Br J Psychiatry 2011;199(5):380-385). A single gene consists of 2 parts: one from mother and one from father. One abnormal component of the COMT gene increases the risk for schizophrenia among cannabis users. (Estrata et al. Acta Psychiatr Scan 2011;123(6):485-9
492) There are also other genetic abnormalities that link schizophrenia and cannabis, including abnormalities of the AKT1 gene and the NRG1 gene. What must be remembered is that the association between using cannabis and schizophrenia is not well understood and not every user will develop chronic depression or schizophrenia. In fact, the majority of users will not develop psychosis. However, the link is strongest in people who start using marijuana during adolescence and they are more likely to develop psychosis later in life. The risk is dose-related. Learning problems and school performance/job performance: Early-age initiation and continued use of marijuana affects memory, attention and ability to think clearly, making it difficult to concentrate, learn new things, and make sound decisions (Dougherty DM et al, Psychopharmacology 2013;226(2):307-319). As a result school performance is impaired. This is associated with increasing number of absences and increasing the risk of dropping out of school. In Washington State, the Healthy Youth Survey results for 2012 found that high school students who used marijuana were more likely to get lower grades in school (Cs, Ds, or Fs) compared to those that do not use. It is difficult to distinguish whether this is due to learning difficulties and lack of motivation or because marijuana users mix with peers who may be involved in a range of risk-taking behaviors. However, marijuana use at an early age is independently associated with learning problems. (Crean RD et al. J Addict Med. 2011;5(1):1-8). It is clear that using marijuana impairs critical thinking for days after use and therefore, many students may be performing below their expected ability. Loss of IQ: Recent reports show that fewer teens and young adults believe that cannabis is harmful to health. Subsequently they are beginning to use cannabis at a younger age and more frequently. In view of this change in behavior a long-term epidemiological study was performed using data collected on over 1000 participants over a 38-year period. The results revealed that users had more cognitive problems and a decline in IQ over the study period (average 8 points). The problems were more severe in users who started marijuana during adolescence. (Meier M. Proc Natl Acad Sci USA 2012;109(40):E2657-2664). Other studies have confirmed that teens who are chronic marijuana users have reduced problem solving skills and exhibit cognitive inflexibility. (Egerton A et al. Neuropsychopharmacology 2005;30(10):1895-18905) 10
Memory loss and changes in brain structure: Persistence use of cannabis in adolescents is associated with defects in both short and long-term memory. Researchers have suggested that these problems are related to structural changes in the parts of the brain that play an important role in memory. A recent scientific study of patients with poor memory function and schizophrenia who persistently smoked marijuana was completed. All patients in the study underwent MRI brain surface mapping. This unique study compared findings in 4 groups of patients with poor memory function documented by neuropsychological testing: the groups included 2 populations, one with schizophrenia and one without schizophrenia. The groups were subsequently divided into 2 subsets, those who smoked marijuana (but did not use marijuana for the preceding 6 months) and those who never used marijuana. It is known that patients with schizophrenia exhibit structural changes in the brain. These same changes were present in study patients who did not have schizophrenia but chronically smoked marijuana and were most severe in schizophrenic patients who smoked marijuana (Smith MJ et al., Schizophrenia Bulletin 2014;40:287-299) Future addiction: Substance abuse during childhood and adolescence is linked to substantial long-term poly-drug addiction. This effect may be related to dopamine in the reward centers of the brain. (Agrawal, Psychol Med 2004;34:1227-37) Early (aged 12 to 14) and late (aged 15 to 17) adolescence is generally regarded as a critical risk period for beginning to use alcohol, marijuana, cocaine, psycho-stimulants and inhalants. The risk of becoming a long-term addict is greater for individuals who begin to use these substances in adolescence than for those who begin to use during adulthood. The 2012 National Survey on Drug Use and Health revealed that among those adults who first tried marijuana at the age of 14 or younger, 13.2 percent were classified as addicts. The rate of addiction was 6 times higher than that for adults who first used marijuana at the age 18 or older. (SAMHSA, 7-17-14, http://samhsa.gov/data/2k14/teds142/sr142-initiationage-2014.htm) Withdrawal: There is a recognized set of withdrawal symptoms that include irritability, difficulty sleeping, craving, anxiety, and discontent. The symptoms typically start after the first week of abstinence and resolve in a few weeks. They are not medically significant but make quitting difficult and contribute to relapses. (Danovitch, Psychiatric Clin NA 2012;35(2):309-326) 11
Conclusion 1. The regular use of THC during adolescence is associated with an increased risk of significant health problems including psychosis 2. The relationship between marijuana and psychological problem is complex which makes studying these problems most difficult. 3. The effects of marijuana on health are determined by its pharmacologic properties, availability and social acceptability. It has been proven over and over, the more available the drug, the greater the risks! 12