1. A Review on Medical Marijuana
Nassima Ait-Daoud Tiouririne, M.D.
Associate Professor
University of Virginia

2. Disclaimer
No financial conflict to report

3. Terminology: Cannabis vs Marijuana
Cannabis refer to a psychoactive product that is derived from the cannabis plant. It contains varied degrees of tetrahydrocannabinol (THC)
Cannabis the drug is produced from the Cannabis sativa or Cannabis indica plant
Marijuana refers to the product that is made from dried flowers and leaves of the cannabis plant
Hemp: generally harvested from a subspecies of the Cannabis genus, which has virtually no psychoactive properties. It is used as a source of industrial, food and other non-drug products
Varieties of Nahuatl are spoken by an estimated 1.5 million Nahua people
The word marijuana, with its current meaning, is said to come from Mexican Spanish, which then spread to other Spanish-speaking nations, and then made its way into English, and other languages as well. Marijuana, which means "Maria" (Mary) and "Juana" (Joan or Jane), is sometimes misspelled as marihuana or mariguana.
However, the Oxford English Dictionary says that the term comes from the Nahuatl word mallihuan, which means "a prisoner". Nahuatl is the language spoken by the Aztecs of Mexico. Some linguists dispute this connection between the Nahuatl word and the term marijuana.
The Oxford English Dictionary says that the term "marijuana" came into usage in the English language at the end of the 19th century.
“Marijuana consists of the dried flowers and subtending leaves and stems of the female Cannabis plant. “
and Cannabis?
Professor Raphael Mechoulam of the Hebrew University in Jerusalem suggests the following etymology for cannabis: The Greek word kannabis from the Arabic word kunnab from the Syriac word qunnappa from the word Hebrew pan nag which came from the Sanskrit word bhanga and the Persian word bang Machoulam suggests that pannag mentioned in the Book of Ezekiel (27:17), is in fact Cannabis.
In the King James Bible, the verse is as follows:
“Judah, and the land of Israel, they [were] thy merchants: they traded in thy market wheat of Minnith, and Pannag, and honey, and oil, and balm.”
R. Mechoulam, W.A. Devane, A. Breuer, J. Zahalka, A random walk through a cannabis field, Pharmacology Biochemistry and Behavior, Volume 40, Issue 3, November 1991, Pages Available online: Accessed 5 May 2011
Tox Talk - Erowid: cannabis

4. Cannabis Facts Cannabis is used in three main forms:
Marijuana is made from dried flowers and leaves of the cannabis plant. It is the least potent of all the cannabis products and is usually smoked or made into edible products like cookies or brownies.
Hashish is made from the resin (a secreted gum) of the cannabis plant. It is dried and pressed into small blocks and smoked. It can also be added to food and eaten.
Hash oil: the most potent cannabis product, is a thick oil obtained from hashish. It is also smoked.

5. Copyright © 2015 American Medical Association. All rights reserved.
From: Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems: A Clinical Review
JAMA. 2015;313(24): doi: /jama
Table Title:
Common Cannabis Preparations
Date of download: 7/13/2015
Copyright © 2015 American Medical Association. All rights reserved.

6. Tincture: (Nabiximol)
Dried flowers
Hashish
Tincture: (Nabiximol)
Kief: cannabis trichomes
Hashish is a concentrated resin cake or ball produced from pressed kief, the detached trichomes and fine material that falls off of cannabis flowers and leaves
Tincture: Cannabinoids can be extracted from cannabis plant matter using high-proof spirits to create a tincture, Nabiximol is a branded product name from a tincture manufacturing
pharmaceutical company
Hash oil is obtained from the cannabis plant by solvent extraction
Infusion: The plant material is mixed with the solvent
Infusion (dairy butter)
Pipe resin
Joint
Hash oil

7. Basic Pharmacology THC is absorbed through the lungs
Causes rapidly rising levels of THC in blood plasma
After peak levels are reached, Plasma THC levels begin to decline
Metabolism by liver
Accumulation of the drug in fat stores

8. Basic Pharmacology Oral consumption of marijuana
Leads to prolonged but poor absorption of THC
Results in low and variable plasma concentrations
Probably due to degradation in stomach, and first pass metabolism by the liver.
THC is converted into several metabolites
11-hydroxy-THC
11-nor-carboxy-THC (THC-COOH)
These metabolites are excreted in feces and urine
Blood levels of marijuana decline quickly
But elimination from the body is much slower.
The drug persists in fatty tissue
Sensitive urine screening tests can detect THC-COOH more than 2 weeks following last use.

9. A typical joint consists of around 0.5 grams to 1 gram of cannabis.
THC content can be around 4% or higher
If about 4% then a 1 gram joint contains about 40 mg of THC
Burning causes the THC to vaporize and enter the smokers lungs in small particles
Only about 20% of the original THC content gets absorbed
There can be substantial variation in the amount of THC absorbed based on
The potency of the marijuana
The amount smoked
The pattern of smoking
I make a habit of asking my patients exactly QUANTITY they’re using, FREQUENCY, ROUTE of administration, WEIGHT used monthly.

10. What is cannabis the drug
Plant > 400 chemicals; > 60 Phytocannabinoids
Δ-9-Tetrahydrocannabinol (THC) was isolated in 1964 and the nonpsychoactive cannabidiol (CBD) in 1963; the ratio in botanical and pharmaceutical preparations determines therapeutic vs psychoactive effects, with the latter emerging when THC is higher in concentration
The principal psychoactive constituent of cannabis is THC; others include: cannabidiol (CBD), cannabinol (CBN), tetrahydrocannabivarin (THCV), and cannabegerol (CBG).

11. Mechanisms of Action
THC is a CB1 (brain) and CB2 (peripheral tissues) agonist
Cannabidiol (CBN) acts as an allosteric modulator of the mu and delta opioid receptors
THC directly inhibit the release of multiple neurotransmitters including acetylcholine, dopamine, and glutamate while indirectly affecting γ-aminobutyric acid, N-methyl-d-aspartate, opioid, and serotonin receptors

12. CB1 receptors CB1 receptors are found primarily in the brain:
Basal ganglia
Limbic system including the hippocampus
Hypothalamus (appetite)
Cerebellum
Male and female reproductive systems
rostral ventrolateral medulla oblongata (RVLM)
CB1 receptors appear to be responsible for the euphoric and some anticonvulsive effects of cannabis.
The CB1 receptor is expressed pre-synaptically at both glutaminergic and GABAergic interneurons and acts as a neuromodultor to inhibit release of glutamate and GABA

14. CB2 CB2 receptors are predominantly found in the immune system
CB2 receptors appear to be responsible for the anti-inflammatory and possibly other therapeutic effects of cannabis

15. Phytocannabinoids
Cannabinol (CBN) is the primary product of THC degradation, and there is usually little of it in a fresh plant. It is only mildly psychoactive. Its affinity to the CB2 receptor is higher than for the CB1 receptor
Cannabidiol (CBD) is not psychoactive. CBD has little affinity for CB1/CB2 receptors but acts as an indirect antagonist of cannabinoid agonists. It may act as act as a 5-HT1a receptor agonist

18. DEA- Schedule I Substance
The Drug Enforcement Administration (DEA) with FDA concurrence, support placement of marijuana in Schedule I [21 U.S.C. 812(b)(1)]
1. Marijuana: high potential for abuse, and no currently accepted medical use in treatment.
2. Lacks accepted safety for use under medical supervision.
3. Sound evidence that smoked marijuana is harmful.

19. What it all means…
Federal vs. State Laws: federal law trumps. Federal law doesn’t permit marijuana sale and usage because its DEA status.
Marijuana must be grown, sold, used, and taxed all within the state
Cannot use any federal land or means of commerce.
They cannot use banks which are federally regulated.
They cannot deduct business expenses on their federal income taxes.
No use of water from federally managed resources.
Recreational Marijuana Legalization:
No criminal penalties for any purpose
Source of taxation and control by the state
You can't be arrested, ticketed, or convicted for using marijuana, if you follow the state laws as to age, place, and amount for consumption
Medical Marijuana Legalization:
Qualifying patients with terminal or debilitating medical conditions who, in the judgment of their health care professionals, may benefit from the medical use of cannabis
Patients shall not be arrested, prosecuted, or subject to other criminal sanctions or civil consequences under state law based solely on their medical use of cannabis
They have to carry a medical marijuana card.
It’s yet another source of taxation and control by the state
Decriminalization:
No criminal and monetary penalties for possessing any amount of marijuana,
Individuals caught with small amounts of marijuana for personal consumption won’t be prosecuted and won’t subsequently receive a criminal record or a jail sentence.
No taxation, no control by local state.
Drug cartels rip all the benefit of the sale of marijuana instead of the state.

20. Medical marijuana is currently legal in 23 states and the District of Columbia, and 17 have moved to decriminalize the drug to varying degrees

21. As a psychiatirst, an addiction specialist and a parent, this is why I worry about marijauna legalization
Dr. Volkow et al. NEJM2014;370:

22. Who Uses? Compare 12-17 yr olds Past Month Use in States With/Without Marijuana As Medicine
Prevention
To a considerable degree, the determinant of use are often specific to each drug.
These determinants include perceived benefits and perceived adverse outcomes that young people come to associate with each drug.
Word of the supposed benefits of using a drug usually spreads much faster than information about the adverse consequences.
Supposed benefits take only rumor and a few testimonials, the spread of which have been hastened and expanded greatly by the media and the Internet. It usually takes much longer for the evidence of adverse consequences (e.g.,adverse reactions, death, disease, overdose, addiction) to cumulate and then be disseminated.
Gene trational Forgetting” Helps Keep the Drug Epidemic Going
There tends to be a continuous flow of new drugs onto the scene and of older ones being rediscovered by young people.
Many drugs have made a comeback years after they first fell from popularity, often because knowledge among youth of their adverse consequences faded as generational replacement or getting.
”Examples include LSD and methamphetamine, two drugs used widely in the 1960s that made a comeback in the 1990s after their initial popularity faded as a result of their adverse consequences becoming widely recognized during periods of high use.
Heroin, cocaine, PCP, and crack are some others that have followed a similar pattern. LSD, inhalants, and ecstasy have all shown some effects of generational forgetting in recent years—that is, perceived risk has declined appreciably for those drugs—which puts future cohorts at greater risk of having a resurgence in use.
In the case of LSD, perceived risk among 8th graders has declined noticeably, and more students are saying that they are not familiar with the drug.
It would appear that a resurgence in availability (which declined very sharply after about 2001, most likely due to the FDA closing a major lab in 2000) could generate another increase in use.
Because of the lag times described previously, thef orces of containment are always playing catch-up with the forces of encouragement and exploitation.

23. Potency
THC is indicative of potency and the concentration of THC has markedly increased over the years (1% to 13% now)

25. What do we really know?

26. Risk of Addiction
9% of experimenters will meet dependence criteria (2.7 million)
16% in those who start as teens (2-4x as likely to be dependent within 2 years of first use)
25-50% in daily smokers
approximately 9% of those who experiment with marijuana will become addicted (according to the criteria for dependence in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM-IV]). The number goes up to about 1 in 6 among those who start using marijuana as teenagers and to 25 to 50% among those who smoke marijuana daily.
According to the 2012 National Survey on Drug Use and Health, an estimated 2.7 million people 12 years of age and older met the DSM-IV criteria for dependence on marijuana, and 5.1 million people met the crite- ria for dependence on any illicit drug1 (8.6 million met the criteria for dependence on alcohol1).
There is also recognition of a bona fide cannabis withdrawal syn- drome5 (with symptoms that include irritability, sleeping difficulties, dysphoria, craving, and anxiety), which makes cessation difficult and contributes to relapse.
As compared with persons who begin to use marijuana in adulthood, those who begin in adolescence are approximately 2 to 4 times as likely to have symptoms of cannabis dependence within 2 years after first use.
Adolescents’ increased vulnerability to adverse long-term outcomes from marijuana use is probably related to the fact that the brain, including the endocan- nabinoid system, undergoes active development during adolescence.

27. Marijuana and Brain Development
The endocannabinoid system (ECS) has been detected from the earliest embryonal stages and throughout pre‐ and postnatal development; endocannabinoids, notably are also present in maternal milk

28. Endocannabinoids During Parental Brain Development
Cannabinoids in brain are implicated in brain development:
promote birth of new brain cells
tell cells what type to become
guide them to their targets
help them form connections

29. The Endocannabinoid System During Development
Perinatal manipulation of EDS, by administering cannabinoids or by maternal marijuana consumption, alters neurotransmitter and behavioral functions in the offspring. Interestingly, the consequences of prenatal cannabinoids are similar to many effects of prenatal stress

30. Miswiring the brain: THC disrupts cortex development in fetus (Tortoriello et al., The EMBO J 2014)
THC reorganizes wires in the developing and adult nervous systems (Kano et al, 2009, Keimpema et al, 2010).
THC impacts cortical wiring in the fetal cerebrum.
THC disrupts development and maintenance of connections critical for highly ordered executive and cognitive functions (Kittler et al, 2000).
due to its unequivocal impact on the establishment of synaptic connectivity in neuronal networks underpinning memory encoding, cognition and executive skills. Moreover, abnormal synaptic organization, even if remaining latent for long periods, might be prone to “circuit failure” if provoked. A “double hit” scenario of cortical failure when a labile network advances into a runaway cascade upon a secondary insult therefore might account for the increased incidence of schizophrenia, depression and addiction in offspring prenatally exposed to cannabis (Substance Abuse & Mental Health Service Administration, 2010; Keimpema et al, 2011).

31. Consequences of Miswiring
Abnormal synaptic organization, even if remaining latent for long periods, might be prone to “circuit failure” if provoked. A “double hit” scenario of cortical failure when a labile network advances into a runaway cascade upon a secondary insult therefore might account for the increased incidence of schizophrenia, depression and addiction in offspring prenatally exposed to cannabis (Substance Abuse & Mental Health Service Administration, 2010; Keimpema et al, 2011).

32. Effects of Marijuana on the brain of adolescents
The cerebellum plays a role in balance, psychomotor speed, language generation, rhythm production, inhibition, attention, and memory

33. Cerebellum (vermis 8-10) greatly enlarged.
Adolescent Marijuana Users Have Enlarged Brain Cerebellum: Association with Poor Executive Function
Compare brain size, brain function in heavy adolescent marijuana users (16-18 yr) controls.
Cerebellum (vermis 8-10) greatly enlarged.
More the enlargement, the poorer marijuana users perform on cognitive function.
Marijuana interferes with normal pruning process in this brain region?
Following one month of abstinence, adolescent MJ users had significantly larger posterior cerebellar vermis volumes than non-using controls. These greater volumes are associated with poorer executive and cognitive functioning. Longitudinal studies are needed to examine typical cerebellar development during adolescence and the influence of marijuana use. MJ users had significantly poorer sustained attention, cognitive inhibition, and abstract reasoning
Source: Medina KL, Nagel BJ, Taper SF. Abnormal cerebellar morphometry in abstinent adolescent marijuana users. Psychiatry Research: Neuroimaging 182: , 2010.

34. Marijuana and cognitive function in adolescents
1,037 individuals were followed from birth to age 38.
The adolescent MU demonstrated a drop in their IQ (quotient of intelligence)from childhood “average” to adult “low-average” full-scale IQ. Indeed, the adolescent MU individuals never achieved their predicted trajectory in IQ, even with sustained abstinence in adulthood
(Meier et al., 2012).

36. School Performance and Lifetime Achievement
6.5% of 12th graders daily or near daily use (higher in dropout population)
Since marijuana use impairs critical cognitive functions, both during acute intoxication and for days after use, many students could be functioning at a cognitive level that is below their natural capability for considerable periods of time
Snowball effect, with one failure leading to many
6.5% of students in grade 12 reported daily or near-daily marijuana use, and this figure probably represents an underestimate of use (dropouts have high rates of use). Cognitive ability during acute intoxication and days after use is diminished. Chronic users likely have long term cognitive functioning impairment.
Since marijua- na use impairs critical cognitive functions, both during acute intoxication and for days after use, many students could be functioning at a cogni- tive level that is below their natural capability for considerable periods of time. Although acute ef- fects may subside after THC is cleared from the brain, it nonetheless poses serious risks to health that can be expected to accumulate with long- term or heavy use. The evidence suggests that such use results in measurable and long-lasting cognitive impairments,16 particularly among those who started to use marijuana in early ado- lescence. Moreover, failure to learn at school, even for short or sporadic periods (a secondary effect of acute intoxication), will interfere with the subsequent capacity to achieve increasingly challenging educational goals, a finding that may also explain the association between regular marijuana use and poor grades.
Conflicting studies, some suggesting long term deficits may be reversible and subtle, rather than disabling once someone abstains from use. other studies show that long-term, heavy use of cannabis results in comparison memory and attention persistently worsen with increasing years of regular use (and use during adolescence). Increased dropout rates. Heavy marijuana use has been linked to lower income, greater need for socioeconomic assistance, unemployment, crim- inal behavior, and lower satisfaction with life

37. Daily use of Marijuana before age 17
60% less likely to get their high school diploma than those who've never used pot
Marijuana users' odds of dropping out being about 2.3 times that of non-users.
Eight times more likely to use other illegal drugs in the future.

38. Marijuana and mood
The acute response to cannabis generally includes euphoria and feelings of detachment and relaxation
Continuous smoking is associated with a gradual waning of the positive mood and social facilitating effects of marijuana and an increase in irritability, depression, social isolation, and low motivation
Not all marijuana users experience it (~21%)
Those with mental illness more likely to have the negative consequences

39. Marijuana as a Treatment of Mental Illness?
Some individuals report that marijuana “dulls anxiety or negative feelings”. Using marijuana to treat mood disorders was described in medical writings in the 19th and early 20th.
Marijuana dulls energy and motivation. Activation and engagement are key parts of recovery from depression.
Only case reports, not evidence based

40. Marijuana and Psychosis
There is reasonable evidence that heavy cannabis use, and perhaps acute use in sensitive individuals, can produce an acute psychosis (Paranoia)
Scientific literature indicates general agreement that heavy marijuana use can precipitate schizophrenic episodes but it is unknown if marijuana use can cause the underlying psychotic disorder

41. Mental Health
Regular marijuana use is associated with an increased risk of anxiety, depression, and psychotic illness, and marijuana use can worsen the courses of these disorders as well.
- Patton GC, Coffey C, Carlin JB, Degenhardt L, Lynskey M, Hall W. Cannabis use and mental health in young people: cohort study. BMJ. 2002;325(7374):
- Di Forti M, Marconi A, Carra E, et al. Proportion of patients in south London with first-episode psychosis attributable to use of high potency cannabis: a case-control study [published online February 18, 2015]. Lancet Psychiatry

42. Cannabis and Performance
Acutely administered marijuana impairs cognition (memory and learning, distorted perception, difficultly in thinking and problem-solving, and loss of coordination)
Most behavioral and physiological effects return to baseline levels within 3-5 hours after drug use
Longer term cognitive deficits in heavy marijuana users have also been reported
A study of experienced airplane pilots showed that even 24 hours after a single marijuana cigarette their performance on flight simulator tests was impaired

43. Effects of Acute Smoked Marijuana on Complex Cognitive Performance
Impaired judgment and difficulty carrying out complex mental processes are included among DSM-IV’s diagnostic criteria for marijuana intoxication

44. Accuracy on cognitive tasks were unaltered
Marijuana daily users
Greater difficulties inhibiting inappropriate responding following the high Delta9-THC
Accuracy on cognitive tasks were unaltered
Carl L. Hart et al NEUROPSYCHOPHARMACOLOGY 2001–VOL. 25, NO. 5

45. Gateway Drug?
Early exposure to cannabinoids in adolescent rodents decreases the reactivity of brain dopamine reward centers later in adulthood
THC’s ability to “prime” the brain for enhanced responses to other drugs

46. Medical Marijuana
The accumulated data indicate a potential therapeutic value for cannabinoid drugs, particularly for symptoms such as pain relief, control of nausea and vomiting, and appetite stimulation
Clinical studies of marijuana are difficult to conduct
The medical use of marijuana are not based on particular diseases but on symptoms

47. Cannabis and Pain
Peripheral nerves that detect pain sensations contain abundant receptors for cannabinoids, and cannabinoids appear to block peripheral nerve pain in experimental animals

48. Cannabis and Pain
Available evidence from animal and human studies indicates that cannabinoids can have a substantial analgesic effect.
Encouraging evidence on cancer pain but small sample
For patients with MS with central pain or painful spasms, THC or nabiximols were found to be probably effective for treating MS-related pain or painful spasms.
Smoked marijuana is of unclear efficacy for reducing pain

49. Cannabis and Immunosuppression
THC have immunosuppressive effects which may be beneficial or detrimental
Mice pretreated with THC one day before infection with a sublethal dose of the pneumonia-causing bacteria and then treated again one day after the infection with THC developed symptoms of septic shock and died; control mice that were not pretreated with THC became immune to repeated infection and survived the bacterial challenge. These mice failed to develop immune memory
Little is known about the immune effects of chronic low- dose exposure to cannabinoids
Klein TW, Newton C, Friedman H Resistance to Legionella pneumophila suppressed by the
marijuana component, tetrahydrocannabinol. Journal of Infectious Diseases 169:1177—1179.

50. Cannabis and Immunosuppression
Good news: THC was found to induce cell death in different types of cancer cells that have cannabinoid receptors.
Bad news: it can lead to enhanced growth of tumors that express low to undetectable levels of cannabinoid receptors by specifically suppressing the antitumor immune response. All these studies have been done in vitro and therefore little is known about the immune effects of chronic low- dose exposure to cannabis.

51. Nausea and Vomiting
Cannabinoids are effective in preventing emesis in some patients who are receiving cancer chemotherapy
In a study comparing THC with metoclopramide, all patients received the same dose of cisplatin and were randomly assigned to the THC group or the metoclopramide group.
Results: Complete control of emesis occurred in 47% of those treated with metoclopramide and 13% of those treated with THC.
In 1985, the FDA approved THC in the form of dronabinol for this treatment of nausea and vomiting associated with chemotherapy
Nabilone (Cesamet) and levonantradol were tested in various settings; the results were similar to those with THC. As in the THC trials, nabilone and levonantradol reduced emesis but not as well as other available agents
Gralla RJ, Tyson LB, Borden LB, et al Antiemetic therapy: A review of recent studies and a report of a random assignment trial comparing metoclopramide with delta-9-tetrahydrocannabinol. CancerTreatment Reports 68:163—172.

52. Appetite Stimulation
In 1992, the FDA approved THC, under the trade name Marinol (dronabinol), as an appetite stimulant for the treatment of AIDS-related weight loss
Dronabinol was associated with an increase in appetite and stable weight, in patients with wasting syndrome associated with AIDS
The profile of cannabinoid drug effects suggests that they are promising for treating wasting syndrome in AIDS patients.

53. Reproductive System
In both male and female animals and humans, THC injections suppress reproductive hormones and behavior
Injections of THC result in rapid, dose-dependent suppression of sex hormones and embryo implantation appears to be inhibited.
The animal and human studies are based on acute treatments (single injections) or short term treatments

54. Multiple Sclerosis: Systematic Review
Most drug tested including oral THC, CBD and Nabiximols found probably effective for reducing patient-reported symptoms probably ineffective for reducing objective measures Smoked marijuana is of uncertain efficacy (insufficient evidence).
Smoked marijuana is of uncertain efficacy (insufficient evidence).
Carefully designed clinical trials testing the effects of cannabinoids on muscle spasticity should be considered
Systematic review: Efficacy and safety of medical marijuana in selected neurologic disorders. Report of the Guideline Development Subcommittee of the American Academy of Neurology.
Barbara S. Koppel, et al Neurology April 29, 2014 vol. 82 no

55. Charlotte’s Web
Charlotte suffers from a rare disorder known as Dravet’s syndrome. She had as many as 300 grand mal seizures a week, was confined to a wheelchair, went into repeated cardiac arrest and could barely speak. Now Charlotte is largely seizure-free, able to walk, talk and feed herself, with her parents attributing her dramatic improvement to this strain of medical cannabis. 

56. Epilepsy
Studies in animal models have shows CBD works as an anticonvulsant
A new international, multi-center study led by researchers from UCSF Benioff Children’s Hospital is the first to evaluate whether purified cannabinoid is effective in treating severe forms of childhood epilepsy that do not respond to standard antiepileptic drugs
The drug, called Epidiolex, is a purified cannabinoid that comes in a liquid form containing no tetrahydrocannabinol (THC)

57. Epidiolex Results
23 patients with treatment-resistant epilepsies, (average age of 10), were enrolled in two epilepsy centers at New York University and the University of California San Francisco.
After establishing a 4-week baseline of frequency, type of seizures and existing antiepileptic drug (AED) regimes, patients received a purified 98% oil-based CBD extract, of known and constant composition at a dose of 5mg/kg/day in addition to their baseline AED regimen. The daily dose was gradually increased until intolerance occurred or a maximum dose of 25 mg/kg/day was achieved.
After three months of therapy, 39% of patients had a greater than 50% reduction in seizures with a median reduction of 32%.
Seizure freedom occurred in 3/9 Dravet patients and 1/14 patients with other forms of epilepsy.
Adverse effects were mostly mild or moderate and included somnolence, fatigue, AED level increases, decreased appetite, weight gain, diarrhea, increased appetite and weight loss.

58. To summarize…

59. Consequences of Marijuana Abuse
Acute (present during intoxication)
Impairs short-term memory
Impairs attention, judgment, and other cognitive functions
Impairs coordination and balance
Increases heart rate
Psychotic episodes
Persistent (lasting longer than intoxication, but may not be permanent)
Impairs memory and learning skills
Sleep impairment
Long-term (cumulative effects of chronic abuse)
Can lead to addiction
Increases risk of chronic cough, bronchitis
Increases risk of schizophrenia in vulnerable individuals
May increase risk of anxiety, depression

60. definite association with with substantial adverse effects, some of which have been detrained with a high level of confidence. Addiction is real. Cognitive impairment is real (specifically memory and perception of time). Motor impairment is real and these effects can have detrimental consequences (MVA). Use during adolescence may result in long lasting changes in brain function that can jeopardize educational, professional and social achievements.
Effects of a drug (legal or not) on health are determined not only by its pharmaco- logic properties but also by its availability and social acceptability. (alcohol and tobacco) offer a sobering perspec- tive, accounting for the greatest burden of dis- ease associated with drugs77 not because they are more dangerous than illegal drugs but because their legal status allows for more widespread ex- posure.
hypothesize that its use will increase and that, by extension, so will the number of persons for whom there will be negative health consequences
the burden on the healthcare system will be REAL. where does this put cannabis on the legalization spectrum?

61. Why not FDA approved?
Scientific evidence to date is not sufficient for the marijuana plant to gain FDA approval, for two main reasons.
Not enough clinical trials as its difficult to get approved.
A substance must have well-defined and measureable ingredients that are consistent from one unit (such as a pill or injection) to the next but cannabis has 100 of variable compounds with different action. Use of defined cannabinoids permits a more precise evaluation of their effects
However, pure THC-based drugs are already FDA approved and prescribed
Dronabinol (Marinol®) and Nabilone (Cesamet®) for nausea and pain associated with cancer chemotherapy and stimulating appetite in patients with wasting syndrome.
Sativex for the relief of cancer-associated pain and spasticity and neuropathic pain in multiple sclerosis.

62. Does Marijuana Fulfill FDA Criteria
Purity: No
Dosage forms: No
Quality control: No
Clinical trials: limited
Safety, side effects: limited

63. Monitoring for Purity
After analyzing more than 600 samples of bud provided by certified growers and sellers, a state license lab detected little medical value and lots of contamination.
Several marijuana flowers were "crawling" with up to 1 million fungal spores.
The 600-plus weed samples generally carried little or no CBD. The average CBD amount: 0.1 percent, the study reports.

64. Cannabinoid Dose and Label Accuracy in Edible Medical Cannabis Products
Ryan Vandrey, PhD1; Jeffrey C. Raber, PhD2; Mark E. Raber2; Brad Douglass, PhD3; Cameron Miller, MS3; Marcel O. Bonn-Miller, PhD4
JAMA. 2015;313(24): doi: /jama

65. Copyright © 2015 American Medical Association. All rights reserved.
From: Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States,
JAMA Intern Med. 2014;174(10): doi: /jamainternmed
Figure Legend:
Association Between Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in Each Year After Implementation of Laws in the United States, Point estimate of the mean difference in the opioid analgesic overdose mortality rate in states with medical cannabis laws compared with states without such laws; whiskers indicate 95% CIs.
Date of download: 7/13/2015
Copyright © 2015 American Medical Association. All rights reserved.

66. Copyright © 2015 American Medical Association. All rights reserved.
From: Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States,
JAMA Intern Med. 2014;174(10): doi: /jamainternmed
Figure Legend:
Mean Age-Adjusted Opioid Analgesic Overdose Death RateStates with medical cannabis laws compared with states without such laws in the United States,
Date of download: 7/13/2015
Copyright © 2015 American Medical Association. All rights reserved.

67. Conclusion
Medical marijuana use is now common in clinical practice in many states, and it is critical for health care providers to understand both the scientific rationale and the practical implications of medical marijuana laws.
Medical marijuana and cannabinoids have significant health risks as well as many potential medical benefits.
While medical marijuana has been at times a controversial and contentious issue, mental health providers have a responsibility to provide evidence-based guidance on this important issue.

68. Thank you

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