HYDROCODONE
RESCHEDULING AND MEDICAL
MARIJUANA
Lynn R. Webster, M.D.
Vice President of Scientific Affairs
PRA Health Sciences
Salt Lake City, UT
LRWebsterMD@gmail.com
(801) 892-5140
www.LynnWebsterMD.com
Twitter: @LynnRWebsterMD
12-Month Financial Disclosures
• AstraZeneca
• Mallinckrodt
• Cara Therapeutics
• Marathon Pharmaceuticals
• Charleston Laboratories
• Merck
• Collegium Pharmaceuticals
• Orexo
• Depomed
• Pfizer
• Egalet
• Inspirion Pharmaceuticals
• Insys Therapeutics
• Kaléo Pharmaceuticals
Updated 10/1/15
• Proove Biosciences
• Signature Therapeutics
• TEVA
• Trevena
• Zogenix
The Impact of Hydrocodone
Rescheduling in People With Pain:
The First 100 Days
Jan F. Chambers1, Rae Marie Gleason1, Kenneth L. Kirsh2,
Bob Twillman3, Lynn Webster4, Jon Berner5, Steven D. Passik2
1National
Fibromyalgia & Chronic Pain Association (NFMCPA); 2Millennium Research Institute; 3American Academy of
Pain Management; 4PRA Health Sciences; 5Woodinville Psychiatric
Background
•
On October 6, 2014, the DEA rescheduled hydrocodone products from
Schedule III to Schedule II in an effort to curb abuse
•
The NFMCPA partnered with health care professionals (HCPs), PRA
Health Sciences, the AAPM, and MRI to create a survey to track the
rescheduling consequences on patients’ lives during the first 100 days
Abbreviations: AAPM, American Academy of Pain Management; DEA, Drug Enforcement Administration; MRI, Millennium Research Institute.
Materials and Methods
• Survey
• Cross-sectional, anonymous, blinded
• IRB approved through Aspire IRB, Santee,
California
• Administered online via SurveyMonkey®
• Explored patients’ experiences after
hydrocodone rescheduling
Abbreviation: IRB, institutional review board.
Materials and Methods (cont’d)
• Participants
• Recruited via newsletters, e-mails, Web pages, and social media by the NFMCPA, the U.S.
Pain Foundation, and other patient organizations
• Eligibility requirements
• >18 years of age
• Had been prescribed hydrocodone
• Survey dates
• Launched: February 5, 2015
• Closed: April 3, 2015
Respondent Demographics
Primary Pain Site
6420 Total Participants
53%
90% Caucasian 59% Married
19%
61% Private
Insurance
90% Women
82% At Least
Some College
Global body
Leg
Lower back
Pelvis
Neck
Other
Respondent Demographics (cont’d)
Age
Employment Status
35
50
% of Respondents
% of Respondents
30
25
20
15
10
40
30
20
10
0
5
0
18-24 25-34 35-44 45-54 55-64 65-74
Age, y
Abbreviations: FT, full-time; PT, part-time.
75+
Duration of Hydrocodone Use
18%
>1 year
1 year or less
82%
• 38% of patients who had been on hydrocodone for at least 1 year had
required at least 1 dose escalation
Hydrocodone Use After Rescheduling
13% borrowed hydrocodone because they
were unable to refill their prescriptions
18% borrowed hydrocodone
to supplement their
prescribed supply
Prescribing Changes After Rescheduling
Change in Hydrocodone Prescribinga
None
Dose lowered
Dose lowered with intent to discontinue
Immediate discontinuation with no substitute
Alternative drug prescribed
a
Most commonly reported changes are shown.
Reponses, No. (%)
2296 (39.0)
501 (8.5)
343 (5.8)
525 (8.9)
873 (14.8)
Changes After Hydrocodone Rescheduling
62% used
marijuana
47%
consumed
alcohol
Hydrocodone
Discontinued
(n=1628)
8% used illicit
drugs
66%
borrowed
medications
Impact of Rescheduling
Impact on Patients
Reponses, No (%)
Increased frequency of HCP visits
3699 (64.2)
Increased expenditures on prescriptions
3301 (57.4)
Increased sense of stigma about being a pain patient
2984 (51.8)
Worsened relationship with HCP
1007 (17.5)
Unable to get prescription filled
883 (15.4)
Experienced withdrawal (difficulty getting pharmacy to fill
prescription)
598 (10.4)
Experienced withdrawal (difficulty physically getting to
pharmacy)
416 (7.2)
Note: Percentages are based on total number of responses for each survey question. Not all participants responded to all questions.
Reasons for Refusal to Fill Prescriptions
Not enough medication in stock
No hydrocodone in stock
National shortage of medication
Pharmacy no longer stocking hydrocodone
No reason given
Pharmacist believed dose was inappropriate
Pharmacist believed medication was inappropriate
Other
0
5
10
15
20
25
30
% of Respondents
35
40
45
Pharmacy Issues
3% of pharmacists
refused to submit
hydrocodone claims to
an insurance company
9% of pharmacists
asked respondents to
pay cash for
prescriptions
Alternative Opioids Prescribed
Other
(30.2%)
Oxycodone
(16.7%)
None
(30.4%)
Tramadol
(22.7%)
Patient Perspectives on Fairness
Patient Perspective on Regulatory Changes
Reponses, No. (%)a
Deny chronic pain patients their right to adequate treatment
4288 (88.0)
Will not hinder addicts in their quest to acquire illegal
prescription drugs
3673 (75.3)
Will not hinder criminals in acquiring and distributing illegal
prescription drugs
3618 (74.2)
Harmful to people with chronic pain
3568 (73.2)
Result in prescription of less effective medications for patients
with chronic pain (so doctors can avoid legal hassles)
3427 (70.3)
Have increased my cost of care
2280 (46.8)
a
Participants could select >1 response.
Missed Work
Increased pain (76%)
Missed Work
Because of
Hydrocodone
Rescheduling
(n=801)
Increased number of HCP visits
(71%)
More time spent getting prescriptions
filled (29%)
Additional Consequences of Rescheduling
19%
27%
Qualitative Data
The hydrocodone rescheduling “makes legitimate chronic pain
sufferers feel as though they are criminals,” and “All we want is to live
life pain-free and be our normal selves again without being treated
like pill addicts.”
Survey Limitations
• Sampling bias
– Recruitment via patient
advocacy Web sites
– May impact generalizability
of findings
• Men not well represented
Conclusions
• Negative consequences of hydrocodone
rescheduling
• Increased pain
• Withdrawal symptoms
• Inconvenience
• Increased cost
• Stigma
• Alienation from physicians and pharmacists
MEDICAL MARIJUANA
Prevalence of Marijuana Use
Lifetime Marijuana/Hashish Use
100%
80%
60%
52%
46%
40%
20%
16%
0%
Ages 12 to 17
Ages 18 to 25
National Institute on Drug Abuse. http://www.drugabuse.gov/drugs-abuse/marijuana. Accessed September 18, 2015.
Ages 26 or Older
Marijuana Substance Abuse
Number of Adolescents Admitted to Publically Funded Substance
Abuse Treatment Facilities on a Typical Day
300
266
250
200
150
100
58
50
12
0
Marijuana
Alcohol
10
3
Heroin or Stimulants Cocaine
Other
Opiates
8
Other
Drugs
Substance Abuse and Mental Health Services Administration. The CBHSQ Report: A Day in the Life of American Adolescents: Substance Use Facts Update.
Rockville, MD: Center for Behavioral Health Statistics and Quality; 2013.
Legal Status of Marijuana
• Illegal at the federal level (classified as Schedule I by the DEA)
Bryn B; American Association for the Advancement of Science. http://www.aaas.org/news/cannabis-new-frontier-therapeutics. Published February 15, 2015. Accessed
September 18, 2015.
Cannabinoids in Marijuana
• >100 cannabinoids in marijuana
• Major cannabinoids: cannabidiol (CBD) and tetrahydrocannabinol (THC)
CBD-type cannabinoids
(noneuphoriant)
Elsohly MA, Slade D. Life Sci. 2005;78(5):539-548.
Δ8-trans-THC-type cannabinoids
(euphoriant)
Trend Toward Increased THC and Decreased CBD in
Illicit Marijuana
Burgdorf JR, Kilmer B, Pacula RL. Drug Alcohol Depend. 2011;117(1):59-61.
Targets of Cannabinoids
Abbreviations: CB1, cannabinoid receptor type 1; CB2, cannabinoid receptor type 2.
Peak Pharmaceuticals. http://peakpharma.com/science/overview/. Accessed September 18, 2015.
Signaling via Central CB1 Receptor
Hill MN, Patel S. Biol Mood Anxiety Disord. 2013;3(1):19.
EVIDENCE IN THE LITERATURE
OF THE EFFICACY AND SAFETY
OF MEDICAL MARIJUANA
CBD Decreased Vomiting Induced by Lithium Chloride
Mean Number of
Vomiting Episodes
Vehicle
(n=14)
*p<0.05 vs other groups in study (not all shown).
Rock EM, et al. Br J Pharmacol. 2012;165(8):2620-2634.
CBD
(n=16)
CBD Attenuated Mucosal Damage in a Human Colonic
Explant Model
Luminal
Epithelial
Damage (%)
Control Incubation IL-17A
Control
Abbreviations: AEA, anandamide; IL, interleukin.
****p<0.0001 vs incubation control; †††p<0.001 vs IL-17A; ††††p<0.0001 vs IL-17A.
Harvey BS, Sia TC, Wattchow DA, Smid SD. Cytokine. 2014;65(2):236-244.
IL-17A
+ AEA
IL-17A
+ hydrocortisone
IL-17A
+ CBD
Summary of Randomized Controlled Studies on
Cannabinoids and Pain
Jensen B, Chen J, Furnish T, Wallace M. Curr Pain Headache Rep. 2015;19(10):524.
Summary of Randomized Controlled Studies on
Cannabinoids and Pain (cont’d)
Jensen B, Chen J, Furnish T, Wallace M. Curr Pain Headache Rep. 2015;19(10):524.
Cannabinoids in Pain, Meta-analysis
Note: Nabiximols contain THC and CBD.
Whiting PF, et al. JAMA. 2015;313(24):2456-2473.
Cannabinoid Safety, Meta-analysis
*Incidence rate = events/person-years. The number of person-years was 445 for cannabinoid exposure and 239 for control.
Wang T, Collet JP, Shapiro S, Ware MA. CMAJ. 2008;178(13):1669-1678.
Cannabinoid Safety, Meta-analysis (cont’d)
*Incidence rate = events/person-years. The number of person-years was 445 for cannabinoid exposure and 239 for control; †For both cannabinoid exposure and
control, all events in this category were classified as “altered mood”; ‡Due to myocardial ischemia.
Wang T, et al. CMAJ. 2008;178(13):1669-1678.
Cannabinoid Safety, Meta-analysis (cont’d)
*Classified according to Medical Dictionary for Regulatory Activities.
Wang T, et al. CMAJ. 2008;178(13):1669-1678.
THE IMPACT OF MEDICAL
MARIJUANA ON OPIOID ABUSE
Reductions in Death From Opioid Overdose After Medical
Marijuana Was Legalized
Bachhuber MA, Saloner B, Cunningham CO, Barry CL. JAMA Intern Med. 2014;174(10):1668-1673.
Impact of Medical Marijuana Dispensaries
Treatment Admission for Opioid Pain
Reliever Addiction
Opioid Overdose Deaths
Powell D, Pacula RL, Jacobson M. Do Medical Marijuana Laws Reduce Addictions and Deaths Related to Pain Killers? Cambridge, MA: National Bureau of Economic
Research; 2015.
THE FUTURE OF MEDICAL
MARIJUANA
Evolving Public Opinion
Pew Research Center. http://www.people-press.org/2013/04/04/majority-now-supports-legalizing-marijuana/. Published April 4, 2013. Accessed September 21, 2015.
Options for Improved Regulation
• Hold medical marijuana to the same standards as other drugs
• Standardize
• Ensure quality control
• More consistently control THC and CBD content
Summary/Next Steps for Medical Marijuana
• Cannabinoids are a promising therapeutic option for pain and other
therapeutic areas
• Additional rigorous research is needed
• Legalization facilitates investigations of efficacy and safety
The Painful Truth
• Available now for purchase from online and local
retailers
• Find out more at thepainfultruthbook.com
• Watch for “The Painful Truth” Documentary to be
released late Fall 2015!
Thank You!
LRWebsterMD@gmail.com
Twitter: @LynnRWebsterMD
www.LynnWebsterMD.com