1. The Green Light
Medicinal Cannabis in New York
Authored/Presented by Dave Porter, Pharm.D Candidate
via Albany College of Pharmacy and Health Sciences
Thursday, February 12th, 2015

2. Presentation Outline
• Background
• History
• A Case Study: Charlotte’s Web
• Science and Studies
• Proposed NYS Regulations
• Legal Challenges
• Other Schedule I Research
• Q&A Session
2

3. But First…
• Things I WILL NOT be doing in this presentation:
– Arguing for the legalization of recreational cannabis
– Supporting use of medicinal cannabis by non-patients
– Using street slang like pot, bud, kush, dope, chronic, etc.
• Things I WILL be doing in this presentation:
– Presenting a professional evidence-based viewpoint,
supporting a reclassification of cannabis to Schedule II
– Reviewing published clinical studies
– Reviewing New York’s proposed regulations (2014)
– Withholding personal opinions, unless prompted
3

4. General and Historical Background
• The cannabis plant (Cannabis sativa, C. indica and
C. ruderalis) is an annual flowering herb
– It has more than 60 unique compounds (~480 total)
– Δ-9-tetrahydrocannabinol (THC) is psychoactive
– Cannabidiol (CBD) is not; may oppose some THC effects
• Earliest recorded use of medicinal cannabis (“ma”)
dates back to 2900BC – Emperor Fu Hsi
– Emperor Shen Nung discovers healing property (2700BC)
• Used as sacramental, medicinal or recreational drug
– Arab physician Ibn Wahshiyah – potentially poisonous?
4

5. 5

6. History in the USA
• 1851 – United States Pharmacopoeia (USP) lists Cannabis
sativa as a legitimate drug with many uses
• 1864 – USP described methods of extracting alkaloids
• 1911 – Massachusetts is first State to ban cannabis outright
• 1937 – Marijuana Tax Act placed a tax on cannabis products
• 1970 – Controlled Substances Act; Schedule I classification
• 1996 – California legalizes cannabis for medicinal purposes
• 1998 – 105th Congress upholds Schedule I classification
• 1999 – IOM’s Marijuana and Medicine report
• 2002-2005 – Gonsales vs. Raich trial
• 2012 – WA and CO legalize recreational cannabis
• 2014 – New York passes the Compassionate Care Act 6

7. Case Study – Charlotte Figi
• Charlotte is a 5 year old female with Dravet Syndrome, a
rare and severe form of profoundly treatment-resistant
epilepsy. She suffers ~300 grand mal seizures per week.
Unable to walk, talk and eat independently. Parents have
tried all anti-seizure drugs indicated for Charlotte’s
condition, as well as some experimental ones, to little or no
effect. Brain damage and cognitive decline noted. Last-
line brain surgery or induction of a medical coma?
• Parents found a video of a boy with severe epilepsy treated
and controlled with an oil high in cannabidiol (CBD)
• Parents met with >100 doctors before they found two who
would recommend medicinal cannabis to treat Charlotte7

8. Case Study – Charlotte Figi

9. • Charlotte’s Parents obtained oil (“R4”) high in CBD
– Seizure rate decreased from 300/week to 1-2/week
• High CBD/Low THC cannabis was rare in Colorado
• Parents contacted the Stanley family, who own one
of the largest cannabis dispensaries in Colorado
– They modified one of their existing strains of product to
be even higher in CBD
Case Study – Charlotte Figi
– They called it “Charlotte’s Web”
– Extracted into oils called “Alepsia”
and “Realm Oil” (~30:1 CBD:THC)
– Realm of Caring Foundation

10. Case Study – Charlotte Figi
• Charlotte today:
– Only has 2-3 seizures/month and regained the
ability to walk, talk, eat, and lead a normal life
• “Charlotte’s Web” is now nationally known
– Featured by Dr. Sanjay Gupta (CNN’s Weed)
– 9,000 patients on the waiting list as of
September 2014*

11. Prevalence of Use and Legal Status
• 23 States (plus the District of Columbia and Guam)
have legislature in place for medicinal cannabis
– Some States have legalized it recently, but have no
programs implemented yet (MD, MN, NH, NY)
• Estimates of over 2,000,000* medicinal cannabis
patients in the USA in October 2014
– * Some States have voluntary registration (CA, ME) or do
not have any registration policies (WA)
• 11 States (AL, FL, IA, KY, MS, MO, NC, SC, TN, UT,
WI) have passed laws legalizing some aspect*
11

12. ProCon. Medical Marijuana Pros and Cons. Last updated 11/13/2014. Available from: <http://medicalmarijuana.procon.org/>.

13. Marinol® (Dronabinol, THC) Review*
• MOA:
– Agonist at endogenous cannabinoid receptors CB1 and CB2
– Signal transduction effects through GPCR in the PAG, RVM
and dorsal horn, decreasing excitability of neurons
– May act in the vomiting center to oppose the effects of
serotonin to block the release of NTs that cause emesis
– Acts in lateral hypothalamus to increase appetite
13
• FDA-Approved Indications:
– CINV refractory to first-line antiemetics
– Appetite stimulant for AIDS/cancer-
related anorexia

14. Marinol® (Dronabinol, THC) Review*
• Dose:
– CINV: 5mg/m2 PO 1-3h prior to chemo, then every 2-4h after.
– AIDS/cancer anorexia: 2.5mg PO before lunch and dinner
• Contraindications, Warnings and Precautions:
– CI: allergy to sesame oil
– History of addiction or drug abuse, mental illness*
• Adverse Drug Reactions:
– Psychoactive effects (24% for CINV), dizziness/drowsiness,
hallucinations, anxiety, altered mental state
• Major DDI’s:
– Ethanol (↑absorption, ↑ADR’s), amphetamines (↑BP, ↑HR)

15. The Institute of Medicine Report (1999)
• The Clinton Administration tasked the IOM with
investigating alleged “gateway effects” of cannabis
– Published a 170 page report – Marijuana and Medicine
– “Gateway effect” greatly questioned (tobacco/alcohol)
– Cannabis treats chronic pain and physical symptoms
with a different MOA in the brain than current drugs
– A lack of concrete recommendations and conclusions,
but many statements calling for additional research*
• 15 out of 18 total recommendations!
– “The acute side effects of marijuana use are within the
risks tolerated for many medications” 15

16. Clinical Trial Evidence
• “Cannabis in painful HIV-associated sensory
neuropathy” – Abrams et al. (2007)
• Prospective, randomized placebo-controlled trial
– Adults with HIV and an average baseline daily pain score
of 50mm on the 100mm visual analog scale (VAS)
• 223 screened, 55 randomized, 50 completed (25/25)
– Primary outcome: >30% reduction in VAS pain intensity
– Patients were randomly assigned to smoke 3.56% THC
cannabis cigarettes or placebo cigarettes lacking
alkaloids TID x 5 days
16

17. Clinical Trial Evidence
• Results:
– 50 patients completed the trial
– >30% reduction in pain variables reported by 53% in the
cannabis group vs. 24% in the placebo group (p=0.04)
– Median reduction of pain on the VAS was 34%,
compared to 17% in placebo group (p=0.03)
– Median 72% pain reduction with the first cannabis
cigarette vs. 15% with placebo (p<0.001)
– No serious adverse events were reported
• Mild: Anxiety, sedation, disorientation, confusion, dizziness
• No patients left the study due to adverse effects
17

18. 18Abrams DI, Jay CA, Shade SB, Vizoso H, Reda H, Press S, Kelly ME, Rowbotham MC, Petersen KL. Cannabis in painful HIV-associated sensory neuropathy:
A randomized placebo-controlled trial. Neurology (2007)68:515-521.

19. Clinical Trial Evidence
• “Low-Dose Vaporized Cannabis Significantly
Improves Neuropathic Pain” – Wilsey et al. (2013)
– Double-blinded, placebo-controlled, crossover RCT
• 382 assessed for eligibility, 59 screened, 39 randomized
– Vaporized cannabis (3.53%/1.29% THC) vs. placebo
– Vapor collected in a vaporizer bag with a specially-
designed mouthpiece that allowed repeated, willful
inhalation interruption without loss of vaporized
cannabis
– Primary outcome: 30% decrease in VAS-assessed pain
19

20. Clinical Trial Evidence
• Patients received either low or medium dose or
placebo cannabis at 3 total visits, served as own control
• Dosing was standardized* as much as possible with the
“Foltin Puff Procedure”
• Results:
– 10/38 (26%) of placebo group had VAS reduction of 30%
– 21/37 (57%) of LOW dose group had 30% VAS reduction
• P value = 0.0069; NNT = 3.2
– 22/36 (61%) of MEDIUM dose group had 30% VAS reduction
• P value = 0.0023; NNT = 2.9
– No significant difference between medium and low dose
20

21. 21
Wilsey B, Marcotte T, Deutsch R, Gouaux B, Sakai S, Donaghe H. (2013). Low-Dose Vaporized Cannabis Significantly Improves Neuropathic Pain. J Pain, 14(2):136-48.

22. Clinical Trial Evidence
• “Smoked cannabis for spasticity in multiple
sclerosis” – Corey-Bloom et al. (2012)
– Randomized, placebo-controlled crossover trial
• 196 screened, 37 randomized, 30 completed trial
• Patients could be cannabis-naïve or experienced
– Primary outcome: change in spasticity on the modified
Ashworth scale (a sum of 6 individual joint scores)
• 0 = no increase in muscle tone
• 1 = slight increase (catch and release during motion)
• 2 = slight increase (catch and minimal resistance)
• 3 = more marked increase during motion
• 4 = considerable increase in tone; passive movement difficult
• 5 = rigid flexion and extension
22

23. Clinical Trial Evidence
• Participants smoked either a placebo or a cannabis
cigarette, using the Foltin Puff Procedure
– 3 visits per treatment phase
• Phase 1 was followed by 11-day washout, then
patients crossed over to opposite group for phase 2
• Results:
– Cannabis use decreased spasticity an additional 2.74
points vs. placebo on the modified Ashworth scale
– Cannabis reduced VAS scores by 5.28 points
– 7 dropouts did not affect results in sensitivity analysis*
23

24. Clinical Trial Evidence
24Adapted from Corey-Bloom J, Wolfson T, Gamst A, Jin S, Marcotte T, Bentley H, Gouaux B. Smoked cannabis for spasticity in multiple sclerosis: a
randomized, placebo-controlled trial. CMAJ (2012);184(10):1143-50.

25. 25Corey-Bloom J, Wolfson T, Gamst A, Jin S, Marcotte T, Bentley H, Gouaux B. Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-
controlled trial. CMAJ (2012);184(10):1143-50.

26. Study Limitations
• Small sample sizes in all studies
– Restrictive nature of Schedule I research
• Difficult to blind the subjects
– Not difficult for patients to realize they ingested THC…
• Most studies haven’t included patients who were
cannabis-naïve at onset of trial
– Abrams et al. (2007) and Wilsey et al. (2013) have NIH
authorization to expose naïve patients to cannabis
• Difficult to standardize the cannabinoid doses
– Foltin Puff Procedure used in most clinical trials
26

27. Compassionate Drug Use
• “Compassionate drug use” refers to the treatment of
seriously ill patients using new, unapproved drugs when
no other treatments are available
– Drugs being tested but not yet approved are investigational
drugs and generally only available to clinical trial participants
• “Expanded access programs” (EAP)
– A company sponsoring a drug in late stage clinical trials can
offer an EAP for patients who can’t enroll in a trial
• “Single patient access programs”
– Doctor contacts drug company and inquires about use for
one patient. If the company agrees, the doctor works with
the company to ask the FDA to approve the drug for use 27

28. New York State Bills and Regulations
• New York Assembly Bill A06357
– Introduced 3/26/2013, passed 6/19/2014
– Introduced by Assembly member Richard Gottfried (D)
– Passed Senate on 6/20/2014
– Signed into law by Gov. Andrew Cuomo on 7/5/2014
– Regulations drafted 12/18/2014
• Title 10 of Official Compilation of Codes, Rules and
Regulations of the State of New York was amended
to include §80-1: Medical Use of Marihuana
28

29. Requirements for Prescribers
• Must have a medical license in good standing in NYS
• Must complete a NYSDOH-approved 4 hour course
– This course WILL NOT count for CE credit
– Course must include pharmacology, CI’s, W/P’s, ADR’s,
OD/abuse prevention, DDI’s, dosing, and the approved
products and their routes of administration
– Course would be somewhat similar to a buprenorphine
prescribing course to treat opioid dependence
• Eligible Prescribers may issue Certifications to
eligible Patients and/or Caregivers
– Must include a statement saying other treatment
options have not provided adequate relief to the Patient

30. Requirements for Prescribers
• Prescribers must be qualified to treat ≥1 of the following
chronic health conditions:
1. Cancer
2. HIV/AIDS
3. Epilepsy
4. Neuropathies
5. Amyotrophic lateral sclerosis (ALS)
6. Huntington’s disease
7. Parkinson’s disease
8. Multiple sclerosis (MS)
9. Inflammatory bowel disease (IBD)
10. Damage to spinal cord nervous tissue with intractable spasticity
• The Commissioner may add or remove approved conditions
and must decide by January 2016 to add PTSD, muscular
dystrophy, Alzheimer’s, dystonia, and rheumatoid arthritis

31. Disease-Accompanying Symptoms
• One or more of the conditions must include:
1. Severe or chronic pain causing a substantial limitation
of function
31
2. Severe nausea
3. Seizures
4. Cachexia or wasting
syndrome
5. Severe or persistent
muscle spasms
• The Commissioner may add or remove disease-
accompanying symptoms

32. Prescribing or Recommending?
• Prescribers can’t prescribe medicinal cannabis on
an Official New York State Prescription Blank, but
they can “recommend” it on separate forms
• On the recommendation form must be written:
– Patient-specific information (like a regular prescription)
– Authorized cannabis brand and formulation
– Dosing information for patient’ proper use
– Any limitations to the use of the approved product
– The total amount of product that can be dispensed
• Quantity can NEVER exceed a 30 day supply!
• Prescriber must retain records for 5 years 32

33. 33
Grant I, Atkinson JH, Gouaux B, Wilsey B. Medical Marijuana: Clearing Away the Smoke. The Open Neurology Journal (2012);6:18-25.

34. Requirements for Patients or Caregivers
• Prescriber-issued Certifications expire in ONE year
– Terminally ill certifications last until death or revocation
• Patients or Caregivers must register with NYSDOH
to be added in registry and pay annual fee of $50*
• Dependent Patients may appoint TWO Caregivers
– Each approved Caregiver can have FIVE Patients
– Persons under 18 require approved Caregivers ≥21
• Patient may not vaporize Products in public places
or any place that has banned smoking cigarettes
• Purchasing party must pay cash to buy products34

35. Example Registration Cards (New Jersey)
35

36. Requirements for Manufacturer Applications
• Each Applicant must pay fees to submit Application
– Application fee is a nonrefundable $10,000
– Registration fee is a refundable $200,000, if approved
• Each Manufacturer must submit:
– Standard operating procedures (SOPs)
– Disposal, security and control procedures
– Product details
– Architecture plans
– Quality assurance plans
– Lab test protocols
36

37. Requirements for Manufacturer Applications
• Must renew Certification every 2 years (same fees)
– Renewal must be received no less than FOUR months
before Manufacturer Certification expiration
– Applicant must include all complaints received, SOPs
changes, lab test reports and theft/loss reports
– Applicant must include quality assurance summary for
all Products tested in prior year, and shortage dates
• The Commissioner can reject or void Certifications,
Applications (including renewals) at any time and
without advance notice if NYSDOH believes that
medicinal cannabis endangers public health! 37

38. Requirements for Manufacturers
• FIVE Manufacturers will be established in New York
– NYSDOH expects over 100 Applications
• Each Manufacturer can produce up to FIVE Products
– Samples of which must be retained for future testing
– Must have at least one cannabis Product that is high in
CBD and low in THC (think “Charlotte’s Web”)
– Must have at least one cannabis Product that has an
approximately 1:1 ratio of THC and CBD.
• A Manufacturer may have up to FOUR contracted
Dispensaries, setting a maximum of 20 in the State
38

39. Requirements for Manufacturers
• Manufacturer must be able to ensure the
availability of a ONE YEAR supply of all Products
• All records must be readily available for inspection
• Manufacturers can ONLY hire union workers ≥21!
• Manufacturers must recertify every 2 YEARS!
• Manufacturer may work with
banks to manage taxes and
money accounts*
– In Colorado, suitcases or strong-
box safes stuffed with cash are
delivered to government offices

40. Some Difficulties With Banking
• Financial institutions disallow payment for illegal drugs
– Federal Law states the businesses cannot deposit their
cannabis revenues at their banks (money laundering?)
• 2009 – Deputy AG David Ogden stated companies in
states with legal cannabis won’t be prosecuted
– 2011 – Deputy AG James M. Cole stated this memo wasn’t
intended to shield cannabis companies from the Feds
• 2014 – AG Eric Holder stated banks could work with
cannabis industries and won’t be prosecuted
– Financial Crimes Enforcement Network: banks may choose
– Must still file Federal “suspicious activity reports”
40

41. Approved Medicinal Cannabis Products
• Each brand must have a total THC and CBD
concentration within 5% of labeled value (mg/dose)
• Brand names must be alphanumeric combinations
• Maximum of 10mg THC per dose!
• Approved dosage forms:
– Extract in oil for SL administration
– Extract for vaporization (metered and uniform doses)
– Extract in a capsule for ingestion
– Edible food product only by Commissioner approval
41

42. Approved Products*

43. Approved Medicinal Cannabis Products
• Product label must include ALL these alkaloids:
– Tetrahydrocannabinol (THC)
– Tetrahydrocannabinol acid (THCA)
– Tetrahydrocannabivarin (THCV)
– Cannabidiol (CBD)
– Cannabinadiolic acid (CBDA)
– Cannabidivarine (CBDV)
– Cannabinol (CBN)
– Cannabigerol (CBG)
– Cannabichromene (CBC)
– Any other cannabinoid component at >0.1%
43

44. Auxiliary Labels
• “Medical marihuana products must be kept in the original
container in which they were dispensed and removed from the
original container only when ready for use by the certified
patient”;
• “Keep secured at all times”;
• “May not be resold or transferred to another person”;
• “This product might impair the ability to drive”;
• “KEEP THIS PRODUCT AWAY FROM CHILDREN (unless medical
marihuana product is being given to the child under a
practitioner’s care”); and
• “This product is for medicinal use only. Women should not
consume during pregnancy or while breastfeeding except on the
advice of the certifying practitioner, and in the case of
breastfeeding mothers, including the infant’s pediatrician.”
44

45. Unapproved Medicinal Cannabis Products
• NO RAW PLANT MATERIAL FOR SMOKING!
– NYS is trying to cut down on statewide smoking rates!
• NO RAW PLANT MATERIAL FOR INGESTION!
– Edibles must be premade and prepackaged
• NO FLASHY BRAND NAMES OR ADVERTISEMENTS!
• NO REFERENCES TO 420 CULTURE!
• NO MOLD OR CONTAMINANTS!
• NO ADDITIVES UNLESS PHARMACEUTICAL GRADE!
• NO STATING YOUR PRODUCT IS MOST EFFECTIVE!
45

46. Unapproved Cannabis Products
46

47. Dispensing Facilities (Dispensaries)
• NYS PHARMACIST MUST BE ON SITE WHEN OPEN!
– Must counsel all Patients, like in a pharmacy
– Medication information sheets must be given
• Dispensaries cannot sell non-cannabis products
without prior NYSDOH approval
• No Product, food or drink may be consumed within
• Patients/caregivers must show certification to enter
– May only fill a 30 DAY SUPPLY at a time, and may NOT
break manufacturer packaging
• Must report all sales to NYSDOH 47

48. Dispensary Exterior (New Jersey)

49. Dispensary Interior (California)

50. Dispensing Facilities (Dispensaries)
• Sufficient security measures must safeguard Staff,
Facilities and Products and must include the following:
– Perimeter alarm
– Motion detectors
– Lighting around the perimeter of the facility
– Video cameras at all entries/exits and at product storage
– 24 hour recording capability (≥90 days of storage space)
– A duress alarm (for forced shut down of security)
– A panic alarm (to alert police of emergency situation)
– A hold-up alarm (to signal police to the robbery)
– Automatic voice dialer, that will send prerecorded message
– Failure notification for security (notification within 5 minutes)
– Backup generator for power outages
– Capability to take clear, color photos with 9600dpi resolution
– Back-up alarm system for non-operational hours
50

51. Other States Involve Pharmacists
• Connecticut (2012)
– Only pharmacists can have dispensary licenses
– Pharmacists must check and send records to the PMP
– Dispensary workers must be registered pharmacy techs
• Minnesota (2014)
– Only pharmacists can dispense cannabis to Patients or
Caregivers and counsel on its proper use
• Rhode Island (2006)
– Legal literature safeguarding RPh licensure (counseling)
• Illinois, Maryland, Minnesota, New Hampshire
– Must have a pharmacist sitting on advisory boards 51

52. Miscellaneous Points
• Under NO circumstances can cannabis products
manufactured in New York be taken out of NYS!
• These proposed regulations would sunset SEVEN
years after the approval date if not reapproved
• Cannabis tax of 7% (paid by Facilities)
• Manufacturers can NOT give free samples
• NY Manufacturers can’t dispense from same facility
– AK, HI, MI, MT, NE, OR & WA don’t allow Dispensaries
• No Product may be delivered without DOH approval
• Only female plants can be used for extraction 52

53. So Can I Get Medicinal Cannabis Now?
• NO! These are just proposed regulations, and
although they are expected to pass with minor
changes, infrastructure is currently unimplemented
• Since the passage of the Compassionate Care Act,
three children have died from treatment-resistant
epilepsy complications
– Acting Commissioner of Health Howard A. Zucker has
petitioned the DEA and DOJ to allow for the interim
importation of high CBD cannabis Products into NYS
– Requests in August and September have been ignored
53

54. Some Dollars and Cents
• Medicinal cannabis programs have mixed success
• Successes:
– Arizona received $7.9 million in taxes and fees from April
2011 – June 2012 (cost the state just $2.4M to run)
– Michigan took in $9.9M in 2012, spending just $3.6M
– Oregon siphoned $900K in 2005, Nevada proposed
siphoning $700,000/year for substance abuse education
• Disappointments and failures-to-launch:
– Rhode Island took in $566,655 in fees but spent
$589,086 in the 2011-2012 fiscal year
– New Jersey approved laws in 2010; in 2013, Greenleaf
Compassion Center was the only operating dispensary

55. Summary of Legal Challenges
• Information vs. misinformation
– Fear-mongering (“gateway drug”)
– Supporters sensationalizing benefits
– Internet shock sites and blogs
– Inherent and persistent biases
– YouTube® and Reddit® “activists”
• Topic is very politically charged
– Federal vs. State
– Democrats vs. Republicans
– Boomers vs. Gen X/Millennials
55

56. Summary of Legal Challenges
• Large-scale trials require approval from the FDA
– The FDA is hesitant to allow studies using Schedule I
controlled substances
– The resulting paucity of data prevents the potential
rescheduling of cannabis into Schedules II-V
• Obtaining product for studies is very prohibitive
– National Institute on Drug Abuse (NIDA) is the ONLY legal
body authorized to cultivate large amounts
– Extension site located at the University of Mississippi
– This single site cannot supply enough product for a
large-scale clinical trial (ex. Phase III) 56

57. Summary of Legal Challenges
• California
– Gonsales vs. Raich landmark trial
– SCOTUS ruled that even with favorable State law, the
Federal Government can criminalize medicinal cannabis
production under the Federal Commerce Clause
• Massachusetts
– As recently as 9/2014, DEA agents have visited MDs to
give an ultimatum: sever ties with medicinal cannabis or
have their DEA licenses permanently revoked
• US Attorney General Eric Holder said the Feds will
be laissez-faire (he’s announced his resignation) 57

58. Food for Thought
• Medicinal cannabis is a legal labyrinth
– Using a Schedule I for medical purposes in the USA
– Once a Schedule I, always a Schedule I?
– Surveillance studies are being done to track changes in
cannabis use, gauge side effects from medical treatment,
and judge effectiveness of State programs
• It has catalyzed renewed interest in medical
research with other classes of Schedule I drugs
– MDMA (“ecstasy”)
– Psychedelics
58

59. Budding Research Areas
• Methylenedioxy-methamphetamine (MDMA)
– Potential PTSD treatment, original research halted in
1985
– Physicians, therapists, researchers opposed the DEA
– Currently being used as unauthorized therapy in USA
• Renewed research in PTSD
– A 2010 treatment-resistant PTSD trial (Mithoefer et al.)
• 20 patients, mean 19 years of TR-PTSD, mean 4.2 drug trials
• 2 introductory sessions, then all day/night MDMA or placebo
session (CAPS 4 days later), repeat, then placebo cross over.
– 2013 long-term follow-up with the same patients
• 17/19 patients had long term decrease in CAPS, no serious ADR
59

60. Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L,Doblin R. The safety and efficacy of 3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects
with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. Journal of Psychopharmacology (2011);25(4):439-452.
• Clinical response = >30%
reduction in CAPS
• Stage 1 – Clinical response
was 83.3% (10/12) in
MDMA group versus 25%
(2/8) in placebo group
• Stage 2 – 100% clinical
response rate with former
placebo group members
• All 3 PTSD-disabled
subjects returned to work
• F/U: 89% reported
increased wellbeing, 79%
reported less avoidance of
people or places

61. • Average time since last MDMA session = ~3.5 years
• Potential for enduring, clinically meaningful benefit to
MDMA-assisted psychotherapy for TR-PTSD?
• No long-term neurocognitive decline (opposite?)
• No development of substance abuse
Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Doblin R. The safety and efficacy of 3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects
with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. Journal of Psychopharmacology (2011);25(4):439-452.

62. Budding Research Areas
• Psilocybin (Psilocybe sp. mushrooms)
– Treatment of anxiety in terminal illness, PTSD, drug and
tobacco addiction and depression
– The potential use in depression therapy was featured in
a CNN article recently
• Lysergic acid diethylamide/LSD
– Renewed research interest as alcohol and drug abuse
therapy and for anxiety brought on by terminal illness
• Ibogaine (Tabernanthe iboga)
– Anti-addictive properties discovered by NYC heroin circle
– Stimulant; cardiac and CNS effects and long duration62

63. Budding Research Areas
• Mescaline (Peyote & San Pedro cacti)
– Studied in alcohol treatment in Native Americans
– The United States Indian Health Service acknowledges it
as the best treatment for alcoholism in Native Americans
• Dimethyltryptamine/DMT (Ayahuasca)
– Potential for treatment of depression and alcoholism
– Santo Daime and União do Vegetal church members
have lower rates of alcoholism than the general public
• Salvinorin A (Salvia divinorum)
– In animal models, seems to treat opioid addiction
63

64. Schedule I vs. Schedule II Requirements
• Schedule I Controlled Substance
– The drug or other substance has a high potential for abuse
– The drug or other substance has no currently accepted
medical use in treatment in the United States
– There is a lack of accepted safety for use of the drug or other
substance under medical supervision
• Schedule II Controlled Substance
– The drug or other substance has a high potential for abuse
– The drug or other substance has a currently accepted
medical use in treatment in the United States or a currently
accepted medical use with severe restrictions
– Abuse of the drug or other substances may lead to severe
psychological or physical dependence 64

65. Conclusions
• There is a universally acknowledged lack of large
scale, long term medicinal cannabis clinical trials!
• Politics continue to prevent cannabis research
– Reclassification to Schedule II is paramount for more
research to be approved and completed
• New York’s medicinal cannabis regulations, when
approved, will be the strictest in the nation
• Medicinal cannabis paves the way for a renewed
investigation into the medical accuracy and current
application of the Controlled Substances Act (1970)
65

66. Resources
• New York State Department of Health
– www.health.ny.gov/regulations/medical_marijuana/
• The Marijuana Policy Project
– www.mpp.org
• The Multidisciplinary Association for Psychedelic Studies
– www.maps.org
• ProCon
– www.medicalmarijuana.procon.org
• Dave Porter, Pharm.D candidate
– David.Porter@acphs.edu
66

67. 1. Abrams DI, Jay CA, Shade SB, Vizoso H, Reda H, Press S, Kelly ME, Rowbotham MC, Petersen KL. Cannabis in painful HIV-associated sensory
neuropathy: A randomized placebo-controlled trial. Neurology (2007)68:515-521.
2. Ahmet Ulugöl. The Endocannabinoid System as a Potential Therapeutic Target for Pain Modulation. Balkan Med J (2014);31:115-20.
3. Alan Zarembo. Exploring therapeutic effects of MDMA on post-traumatic stress. LA Times: Mar 15, 2014. Available from: <
http://articles.latimes.com/2014/mar/15/local/la-me-mdma-20140316>.
4. Basch E, Prestrud AA, Hesketh PJ, et al. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol
2011;29(31):4189-98.
5. Baumeister D, Barnes G, Giaroli G, Tracy D. Classical hallucinogens as antidepressants? A review of pharmacodynamics and putative clinical
roles. Ther Adv Psychopharmacol (2014);4(4):156-69.
6. Carhart-Harris RL, Leech R, Williams TM, Erritzoe D, Abbasi N, Bargiotas T, et al. Implications for psychedelic-assisted psychotherapy:
functional magnetic resoinance imaging study with psilocybin. British Journal of Psychiatry (2012);200:238-44.
7. Clark PA, Capuzzi K, Fick C. Medical marijuana: Medical necessity versus political agenda. Med Sci Monit (2011);17(12):249-261.
8. Compassionate Care New York. Frequently Asked Questions about New York’s Medical Marijuana Bill. (2014). Compassionate Care New York.
Available from <www.compassionatecareny.org>.
9. Corey-Bloom J, Wolfson T, Gamst A, Jin S, Marcotte T, Bentley H, Gouaux B. Smoked cannabis for spasticity in multiple sclerosis: a
randomized, placebo-controlled trial. CMAJ (2012);184(10):1143-50.
10. Dronabinol, THC. In: Clinical Pharmacology [database on the Internet]. Tampa (FL): Gold Standard; 2008 [updated 6Jan 2014; cited 26 Jan
2015]. Available from: www.clinicalpharmacology.com. Subscription required to view.
11. Dronabinol. In: Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc.; 2013 [updated 15 Jan 2015; cited 27 Jan 2015].
Available from: http://online.lexi.com. Subscription required to view.
12. Ellis RJ, Toperoff W, Vaida F, van den Brande G, Gonzales J, Gouaux B, Bentley H, Atkinson JH. Smoked Medicinal Cannabis for Neuropathic
Pain in HIV: A Randomized, Crossover Clinical Trial. Neuropsychopharmacology (2009);34(3):672-80.
13. Ethan B Russo. Cannabinoids in the management of difficult to treat pain. Ther Clin Risk Manag (2008);4(1):245–59.
14. Food and Drug Administration. Controlled Substances Act. Updated Jun 2009. Available from:
<http://www.fda.gov/regulatoryinformation/legislation/ucm148726.htm#cntlsbb>.
15. Garcia-Romeu A, Griffiths RR, Johnson MW. Psilocybin-Occasioned Mystical Experiences in the Treatment of Tobacco Addiction. Current Drug
Abuse Reviews (2014);7(2):e-pub ahead of print.
16. Gasser P, Holstein D, Michel Y, Roblin R, Yazar-Klosinski B, Passie T, et al. Safety and Efficacy of Lysergic Acid Diethylamide-Assisted
Psychotherapy for Anxiety Associated with Life-threatening Diseases. J Nerv Ment Dis (2014):4(202):513-20. 67
References

68. 17. Gasser P, Holstein D, Michel Y, Roblin R, Yazar-Klosinski B, Passie T, et al. Safety and Efficacy of Lysergic Acid Diethylamide-Assisted
Psychotherapy for Anxiety Associated with Life-threatening Diseases. J Nerv Ment Dis (2014):4(202):513-20.
18. Gerald J McKenna. The Current Status of Medical Marijuana in the United States. Hawai’I J of Med & Pub Health (2014);73(4):105-8.
19. Grob CS, Danforth AL, Chopra GS, Hagerty M, McKay CR, Halberstadt et al. Pilot Study of Psilocybin Treatment for Anxiety in Patients With
Advanced-Stage Cancer. Arch Gen Psychiatry (2011);68(1):71-78.
20. Grotenhermen F, Müller-Vahl K. The Therapeutic Potential of Cannabis and Cannabinoids. Deutsches Ärzteblatt International (2012);109(29–
30):495–501.
21. Gonzalez R, Martin EM, Grant I, Neuropsychology and Substance Use, Taylor & Francis Group. (2007) Marijuana (Chapter 5, 139-170).
22. Grant I, Atkinson JH, Gouaux B, Wilsey B. Medical Marijuana: Clearing Away the Smoke. The Open Neurology Journal (2012);6:18-25.
23. Grant I, Atkinson JH, Mattison A, Coates TJ. Report to the Legislature and Governor of the State of California presenting findings pursuant to
SB847 which created the CMCR and provided state funding. Center for Medicinal Cannabis Research. 2010 Feb 11. Available from:
<www.cmcr.ucsd.edu>.
24. Griffiths RR, Johnson MW, Richards WA, Richards BD, McCann U, Jesse R. Psilocybin occasioned mystical-type experiences: Immediate and
persisting dose-related effects. Psychopharmacology (Berl) (2011);218(4):649-65.
25. Jennifer Donnelly. The Need for Ibogaine in Drug and Alcohol Addiction Treatment. Journal of Legal Medicine (2011);32:93-114.
26. Johnson MW, Garcia-Romeu A, Cosimano MP, Griffiths RR. Pilot study of the 5-HT2aR agonist psilocybin in the treatment of tobacco
addiction. Journal of Psychopharmacology (2014);28(11):983-92.
27. Johnson MW, Richards WA, Griffiths RR. Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology
(2008);22(6):608-20.
28. Joseph Gregorio. Physicians, Medical Marijuana, and the Law. AMA J of Ethics (2014):16(9):732-738.
29. Kahan M, Srivastava A, Spithoff S, Bromley L. Prescribing smoked cannabis for chronic noncancer pain: Preliminary recommendations.
Canadian Family Physician (2014);60:1083-90.
30. Kraehenmann R, Preller KH, Scheidegger M, Pokorny T, Bosch OG, Seifritz E, et al. Psilocybin-induced Decrease in Amygdala Reactivity
Correlates with Enhanced Positive Mood in Healthy Volunteers. Biol Psychiatry (2014);e-pub.
31. Krebs TS and Johansen PO. Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. Journal of
Psychopharmacology (2012):26(3):996-1002.
32. Krebs TS and Johansen PO. Psychedelics and Mental Health: a Population Study. PLoS ONE (2013);8(8):e63972.
33. Lynch ME, Campbell F. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. Br J Clin Pharmacol
(2011);72(5):735-44. 68
References

69. References
34. Mačiulaitis R, Kontrimavičiūtė V, Bressolle FMM, Briedis V. Ibogaine, an anti-addictive drug: pharmacology and time to go further in
development. A narrative review. Human and Experimental Toxicology (2008);27:181-194.
35. Michael Winkelman. Psychedelics as Medicines for Substance Abuse Rehabilitation: Evaluating Treatments with LSD, Peyote, Ibogaine and
Ayahuasca. Current Drug Abuse Reviews (2014);7:101-16.
36. Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Doblin R. The safety and efficacy of 3,4-methylenedioxymethamphetamine-assisted
psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. Journal
of Psychopharmacology (2011);25(4):439-452.
37. Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Martin SF, Yazar-Klosinski, et al. Durability of improvement in post-traumatic stress
disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxy-methamphetamine-assisted
psychotherapy:a prospective long-term follow-up study. Journal of Psychopharmacology (2013);27(1):28-39.
38. Muni Rubens. Political and Medical Views of Medical Marijuana and its Future. Social Work in Public Health (2014);29:121-31.
39. Nabilone. In: Clinical Pharmacology [database on the Internet]. Tampa (FL): Gold Standard; 2008 [updated 21 Jul 2014; cited 26 Jan 2015].
Available from: www.clinicalpharmacology.com. Subscription required to view.
40. Nabilone. In: Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc.; 2013 [updated 20 Nov 2014; cited 27 Jan 2015].
Available from: http://online.lexi.com. Subscription required to view.
41. New York State Assembly Bill 6357. 2013 Mar 26. Available from <http://assembly.state.ny.us/leg/?sh=printbill&bn=A06357&term=2013>.
42. New York State Department of Health. New York State Medical Marijuana Program. Dec 2014. Available from:
<http://www.health.ny.gov/regulations/medical_marijuana/>.
43. ProCon. Medical Marijuana Pros and Cons. Last updated 11/13/2014. Available from: <http://medicalmarijuana.procon.org/>.
44. Schenberg EE,de Castro Comis MA, Rassmussen Chaves B, da Silveira DX. Treating drug dependence with the aid of ibogaine: A retrospective
study. Journal of Psychopharmacology (2014);28(11):993-1000.
45. Tylš F, Páleníček T, Horáčeka J. Psilocybin – Summary of knowledge and new perspectives. European Neuropsychopharmacology
(2014);24:342-56.
46. Wallace M, Schulteis G, Atkinson JH, Wolfson T, Lazzaretto D, Bentley H, et al. Dose-dependent Effects of Smoked Cannabis on Capsaicin-
induced Pain and Hyperalgesia in Healthy Volunteers. Anesthesiology (2007);107(5):785-96.
47. Wilsey B, Marcotte T, Deutsch R, Gouaux B, Sakai S, Donaghe H. (2013). Low-Dose Vaporized Cannabis Significantly Improves Neuropathic
Pain. J Pain, 14(2):136-48.
48. Wilsey B, Marcotte T, Tsodikov A, Millman J, Bentley H, Gouaux B, Fishman S. (2008) A Randomized, Placebo-Controlled, Crossover Trial of
Cannabis Cigarettes in Neuropathic Pain. J Pain, 9(6):506-21.
69

70. 70
Any Questions?
Thanks for Listening!