El problema de la Marijuana
Gabriel Handlarz 2015
An 8000-year time line of cannabis use
around the world
Cannabis
•
•
•
•
•
cannabis is one of the oldest known psychoactive plants
First reported use as medicine > 5000 years ago
Introduced into Western medicine in 1840’s by
Dr. W.B. O’Shaughnessy
One of earliest non-food plants cultivated
– fiber for rope, seeds for oil and birdseed
– mixture of leaves, stems, tops
– 1960’s: 1-3% THC; 1990’s: up to 8-10%
•
Cannabis and British Medicine
•
WB O’Shaughnessy, Professor of Chemistry and
Medicine in the Medical College of Calcutta,
Government Chemical Examiner, Knighted in
1856 (4000 miles of telegraph line)
•
‘Powerful and valuable remedy in hydrophobia,
tetanus, cholera and many convulsive disorders’
Cannabis
• The Bengal Pharmacopoeia and General
Conspectus of Medicinal Plants, (Calcutta 1844).
•
Provincial Medical and Surgical Journal (BMJ)
•
Royal Medico-Botanical Society, London
February 22 1843
• Listed in U.S
Pharmacopeia
1850-1941
• marijuana &
hashish extracts
were the 1st, 2nd, or
3rd most prescribed
meds in the US
from 1842-1890s
gout
rheumatneuralgia
ism
tetanus
hydrophobia
epidemic cholera
convulsions
chorea
hysteria
mental depression
delirium tremens
insanity
uterine hemorrhage
Cannabis for neuropathic pain…in
1906
Cannabis for Neuralgia 1925
And then along came Harry…
Harry Anslinger
• Had NO formal medical training
• Our first drug czar
• Despite being “anti-drug”, he authorized a pharmacist near the White
House to supply morphine for addicted Senator Joseph McCarthy during
the communist crusades.
• Openly prosecuted doctors for over-prescribing, sending some to prison
Single-handedly created “Reefer Madness”
• Anslinger was privately funded by William Randolph Hearst who wanted to
eliminate hemp as an industrial competitor
• This also allowed Anslinger, an avowed racists, to rid the southwest of
Hispanics
•
Prohibition
1937
Chemical classes
Cannabinoids (66)
Nitrogenous compounds (27)
AminoChemical classes
Cannabinoids (66)
Nitrogenous compounds (27)
Amino acids(18)
Proteins/ enzymes (11)
Sugars (34)
Hydrocarbons (50)
Simple alcohols (7)
Simple aldehydes (12)
Simple ketones (13)
Simple acids (21)
Fatty acids (22)
Simple esters/lactones (13)
Steroids (11)
Terpenes (20)
Non-cannabinoid phenols (25)
Flavoroids (21)
Vitamins (1)
Pigments (2)
Elements (9)
Total known compounds (483)
Chemical constituents of
Cannabis
Constituyentes de la Cannabis Sativa
•Los componentes naturales identificados o aislados
se han incrementado a lo largo de las ultimas
décadas
•1980 423 componentes
•1995 485 componentes
•2012 545 componentes
Constituyentes del Cannabis (sativa)
•∆9 -tetrahydrocannabinol (THC)
•∆8 -tetrahydrocannabinol
•Cannabigerol(CBG)
•Cannabichromene (CBC)
•Cannabidiol (CBD)
•Cannabinodiol (CBND)
•Cannabielsoin(CBE)
•Cannabicyclol(CBL) Cannabinol (CBN)
•Cannabitriol (CBT) Miscelaneus
Constituyentes del Cannabis (Sativa)
•Delta 9 THC tiene 18 subtipos
•CBC 8 subtipos
El resto son variantes siendo en total 104
cannabinoides
Hay 441 componentes no cannabinoides
como ser flavonoides, esteroides,
fenantrenes, acidos grasos, compuestos
nitrogenados
Examples of Flowers from Different Clones
“Bubble Gum”
“Big Bud”
“Dutch Northern Lights”
The ingredients of cannabis
•Tetrahydrocannabinol (THC) – partial
agonist at CB1
•High doses cause impairment of
memory and learning,
•hallucinations and paranoid ideas
THC
attention,
•Cannabidiol (CBD) – inverse agonist at CB1
•Is not hallucinogenic
•Has anxiety relieving properties
•Antagonises effects of THC
•Antipsicotico?
CBD
The ingredients of cannabis
•THC causes
•Cannabidiol (CBD)
•Impairment of attention,
memory and learning
•Hallucinations and
paranoid ideas
•Is not hallucinogenic
•Has anxiety relieving properties
•Antagonises effects of THC
THC
CBD
Marijuana as Medicine
Marijuana as Medicine?
Therapeutic Potential:
1) Relieving pain
2) Controlling nausea
3) Stimulating appetite
4) Decreasing ocular pressure
Cannabinoid-based medications:
1) Dronabinol (Marinol®)
2) Nabilone (Cesamet®)
3) Sativex®
Neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol in hypoxicischemic newborn piglets.
Francisco J. Alvarez, Hector Lafuente, M. Carmen Rey-Santano, Victoria E. Mielgo, Elena
Gastiasoro, Miguel Rueda, Roger G. Pertwee, Ana I. Castillo, Julia N Romero, and Jose
Martinez-Orgado - Pediatr Res, 2008. 64(6):p. 653-8.
Cannabidiol reduces brain damage and improves functional recovery after acute
hypoxia-ischemia in newborn pigs.
Lafuente, Alvarez, Pazos, Alvarez, Rey-Santano, Mielgo, Murgia-Esteve, Hilario, MartinezOrgado - Pediatr Res, 2011. 70(3):p.272-7
Mechanisms of cannabidiol neuroprotection in hypoxic-ischemic newborn pigs: Role of
5HT1A and CB2 receptors.
Pazos, Mohammed, Lafuente, Santos, Martinez-Pinilla, Moreno, Valdizan, Romero,
Pazos, Franco, Hillard, Alvarez, Martinez-Orgado - Neuropharmacology, 2013. 71:p. 28291
Diabetes/Enfermedad metabólica
The cannabinoid Δ(9)-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models
of obesity.
Wargent ET, Zaibi MS, Silvestri C, Hislop DC, Stocker CJ, Stott CG, Guy GW, Duncan M, Di Marzo V, Cawthorne
MA. Nutr Diabetes. 2013 May 27;3:e68.
The endocannabinoid system in energy homeostasis and the etiopathology of metabolic disorders.
Silvestri C, Di Marzo V. Cell Metab. 2013 Apr 2;17(4):475-90.
Cannabinoids and Endocannabinoids in Metabolic Disorders with Focus on Diabetes
Di Marzo V, Piscitelli F, Mechoulam R. Handb Exp Pharmacol. 2011;(203):75-104.
Cannabinoids inhibit insulin receptor signalling in pancreatic β-cells
Kim W, Doyle ME, Liu Z, Lao Q, Shin YK, Carlson OD, Kim HS, Thomas S, Napora JK, Lee EK, Moaddel R, Wang
Y, Maudsley S, Martin B, Kulkarni RN, Egan JM. Diabetes. 2011 Apr;60(4):1198-209.
A role for the putative cannabinoid receptor GPR55 in the islets of Langerhans
Romero-Zerbo SY, Rafacho A, Díaz-Arteaga A, Suárez J, Quesada I, Imbernon M, Ross RA, Dieguez C,
Rodríguez de Fonseca F, Nogueiras R, Nadal A, Bermúdez-Silva FJ. J Endocrinol. 2011 Nov;211(2):177-85.
Inflamación/ Enfermedades digestivas
Cannabidiol in inflammatory bowel diseases: a brief overview.
Esposito G, Filippis DD, Cirillo C, Iuvone T, Capoccia E, Scuderi C, Steardo A, Cuomo R, Steardo L. Phytother Res. 2013 May;27(5):633-6.
Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease.
Borrelli F, Fasolino I, Romano B, Capasso R, Maiello F, Coppola D, Orlando P, Battista G, Pagano E, Di Marzo V, Izzo AA. Biochem Pharmacol. 2013
May 1;85(9):1306-16.
Cannabinoids mediate opposing effects on inflammation-induced intestinal permeability.
Alhamoruni A, Wright KL, Larvin M, O'Sullivan SE. Br J Pharmacol. 2012 Apr;165(8):2598-610.
Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation.
De Petrocellis L, Orlando P, Moriello AS, Aviello G, Stott C, Izzo AA, Di Marzo V. Acta Physiol (Oxf). 2012 Feb;204(2):255-66.
Cannabidiol reduces intestinal inflammation through the control of neuroimmune axis.
De Filippis D, Esposito G, Cirillo C, Cipriano M, De Winter BY, Scuderi C, Sarnelli G, Cuomo R, Steardo L, De Man JG, Iuvone T. PLoS One.
2011;6(12):e28159.
Cannabis use amongst patients with inflammatory bowel disease.
Lal S, Prasad N, Ryan M, Tangri S, Silverberg MS, Gordon A, Steinhart H. Eur J Gastroenterol Hepatol. 2011 Oct;23(10):891-6.
Treatment of Crohn's disease with cannabis: an observational study.
Naftali T, Lev LB, Yablecovitch D, Half E, Konikoff FM. Isr Med Assoc J. 2011 Aug;13(8):455-8.
Impact of cannabis treatment on the quality of life, weight and clinical disease activity in inflammatory bowel disease patients: a pilot
prospective study.
Lahat A, Lang A, Ben-Horin S. Digestion. 2012;85(1):1-8.
Gut feelings about the endocannabinoid system.
Di Marzo V, Piscitelli F. Neurogastroenterol Motil. 2011 May;23(5):391-8
Oncología
Enhancing the activity of cannabidiol and other cannabinoids in vitro through modifications to drug combinations
and treatment schedules.
Scott KA, Shah S, Dalgleish AG, Liu WM. Anticancer Res. 2013 Oct;33(10):4373-80.
Cannabidiol as potential anticancer drug.
Massi P, Solinas M, Cinquina V, Parolaro D. Br J Clin Pharmacol. 2013 Feb;75(2):303-12
Cannabidiol, a Non-Psychoactive Cannabinoid Compound, Inhibits Proliferation and Invasion in U87-MG and T98G
Glioma Cells through a Multitarget Effect.
Solinas M, Massi P, Cinquina V, Valenti M, Bolognini D, Gariboldi M, Monti E, Rubino T, Parolaro D. PLoS One.
2013 Oct 21;8(10):e76918.
Cannabinoids: a new hope for breast cancer therapy?
Caffarel MM, Andradas C, Pérez-Gómez E, Guzmán M, Sánchez C. Cancer Treat Rev. 2012 Nov;38(7):911-8
Towards the use of cannabinoids as antitumour agents.
Velasco G, Sánchez C, Guzmán M. Nat Rev Cancer. 2012 May 4;12(6):436-44.
Cannabidiol inhibits angiogenesis by multiple mechanisms.
Solinas M, Massi P, Cantelmo AR, Cattaneo MG, Cammarota R, Bartolini D, Cinquina V, Valenti M, Vicentini LM,
Noonan DM, Albini A, Parolaro D. Br J Pharmacol. 2012 Nov;167(6):1218-31.
Sativex: Multiple Sclerosis
Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis.
Michael G. Serpell, William Notcutt, Christine Collin. J Neurol 2013;260:285-295.
A questionnaire survey of patients and carers of patients prescribed Sativex as an unlicensed medicine.
William G. Notcutt. Prim Health Care Res Dev. 2012 Jul 12:1-8.
Assessments of blinding to treatment allocation in studies of a cannabis-based medicine (Sativex) in people with multiple sclerosis: a new
apporach.
S. Wright, P. Ducombe and D.G. Altman. Trials 2012; 13:189. DOI:10.1186/1745-1625-13-189.
A placebo-controlled, parallel-group, randomized withdrawal study of subjects with symptoms of spasticity due to multiple sclerosis who are
receiving long-term Sativex® (nabiximols).
Notcutt W, Langford R, Davies P, Ratcliffe S, Potts R. Mult Scler. 2012 Feb;18(2):219-28.
The evaluation of the effects of Sativex (1:1 THC BDS:CBD BDS on the inhibition of spasticity in an experimental model of multiple sclerosis.
(Sativex/Baclofen).
A. Hilliard, C. Stott, S.Wright, G. Guy, G. Pryce, S. Al-Izki, C. Bolton, and G. Giovannoni. International Scholarly Research Network ISRN Neurology
Volume 2012;2012:802649.
A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex® ), as add-on therapy, in
subjects with refractory spasticity caused by multiple sclerosis.
Novotna A, Mares J, Ratcliffe S, Novakova I, Vachova M, Zapletalova O, Gasperini C, Pozzilli C, Cefaro L, Comi G, Rossi P, Ambler Z, Stelmasiak Z,
Erdmann A, Montalban X, Klimek A, Davies P; Sativex Spasticity Study Group. Eur J Neurol. 2011 Sep;18(9):1122-31
Randomized controlled trial of Sativex to treat detrusor overactivity in multiple sclerosis.
Kavia RB, De Ridder D, Constantinescu CS, Stott CG, Fowler CJ. Mult Scler. 2010 Nov;16(11):1349-59.
Sativex Cancer Pain
An Open-Label Extension Study to Investigate the Long-Term Safety and Tolerability of THC/CBD
Oromucosal Spray and Oromucosal THC Spray in Patients With Terminal Cancer-Related Pain Refractory to
Strong Opioid Analgesics.
Johnson JR, Lossignol D, Burnell-Nugent M, Fallon MT. J Pain Symptom Manage. 2012 Nov 7. pii: S08853924(12)00439-3.
Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebocontrolled, graded-dose trial.
Portenoy RK, Ganae-Motan ED, Allende S, Yanagihara R, Shaiova L, Weinstein S, McQuade R, Wright S,
Fallon MT. J Pain. 2012 May;13(5):438-49.
Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety,
and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain.
Johnson JR, Burnell-Nugent M, Lossignol D, Ganae-Motan ED, Potts R, Fallon MT. J Pain Symptom Manage.
2010 Feb;39(2):167-79.
Cannabinoids in the management of difficult to treat pain.
Russo EB. Therapeutics and Clinical Risk Management.2008;4(1):245-59.
Cannabis, pain, and sleep: lessons from therapeutic clinical trials of Sativex, a cannabis-based medicine.
Russo EB, Guy GW, Robson PJ. Chem Biodivers. 2007 Aug;4(8):1729-43.
Sativex Neuropathic Pain
A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with
the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis.
Langford RM, Mares J, Novotna A, Vachova M, Novakova I, Notcutt W, Ratcliffe S. J Neurol. 2012 Nov 21.
Cannabinoids in the management of difficult to treat pain.
Russo EB. Therapeutics and Clinical Risk Management.2008;4(1):245-59.
Cannabis, pain, and sleep: lessons from therapeutic clinical trials of Sativex, a cannabis-based medicine.
Russo EB, Guy GW, Robson PJ. Chem Biodivers. 2007 Aug;4(8):1729-43.
Oromucosal delta-9 –tetrahrdrocannabinol/cannabidiol for neuropathic pain associated with Multiple Sclerosis: An
uncontrolled, open-label, 2-year extension trial.
Rog D, Nurmikko TJ, Young, CA. Clinical Therapeutics. 2007;20(9):2068-2079
Randomized controlled trial of cannabis medicine in central pain due to multiple sclerosis.
Rog D, Nurmikko T, et al. Neurology. 2005;65:812-819
Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion:
results of a randomised controlled trial.
Berman JS, Symonds C, Birch R. Pain. 2004;112:299-306.
Trastornos psiquiátricos
Cannabinoids and Schizophrenia: Therapeutic Prospects.
Robson PJ, Guy GW, Di Marzo V. Curr Pharm Des. 2013 Jun 14. [Epub ahead of print]
Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia.
Leweke FM, Piomelli D, Pahlisch F, Muhl D, Gerth CW, Hoyer C, Klosterkötter J, Hellmich M, Koethe D. Transl Psychiatry. 2012
Mar 20;2:e94
Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders.
Campos AC, Moreira FA, Gomes FV, Del Bel EA, Guimarães FS. Philos Trans R Soc Lond B Biol Sci. 2012 Dec
5;367(1607):3364-78.
Neural mechanisms for the cannabinoid modulation of cognition and affect in man: a critical review of neuroimaging
studies.
Bhattacharyya S, Atakan Z, Martin-Santos R, Crippa JA, McGuire PK. Curr Pharm Des. 2012;18(32):5045-54.
Cannabidiol and clozapine reverse MK-801-induced deficits in social interaction and hyperactivity in Sprague-Dawley rats.
Gururajan A, Taylor DA, Malone DT. J Psychopharmacol. 2012 Oct;26(10):1317-32.
Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology.
Bhattacharyya S, Morrison PD, Fusar-Poli P, Martin-Santos R, Borgwardt S, Winton-Brown T, Nosarti C, O' Carroll CM, Seal M,
Allen P, Mehta MA, Stone JM, Tunstall N, Giampietro V, Kapur S, Murray RM, Zuardi AW, Crippa JA, Atakan Z, McGuire PK.
Neuropsychopharmacology. 2010 Feb;35(3):764-74.
Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug.
Zuardi AW, Crippa JA, Hallak JE, Moreira FA, Guimarães FS. Braz J Med Biol Res. 2006 Apr;39(4):421-9.
Epilepsia
Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy.
Porter BE, Jacobson C. Epilepsy Behav. 2013 Dec;29(3):574-7.
Cannabidivarin (CBDV) suppresses pentylenetetrazole (PTZ)-induced increases in epilepsy-related gene
expression.
Amada N, Yamasaki Y, Williams CM, Whalley BJ. PeerJ. 2013 Nov 21;1:e214.
Cannabidivarin is anticonvulsant in mouse and rat.
Hill AJ, Mercier MS, Hill TD, Glyn SE, Jones NA, Yamasaki Y, Futamura T, Duncan M, Stott CG, Stephens GJ,
Williams CM, Whalley BJ. Br J Pharmacol. 2012 Dec;167(8):1629-42.
Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures
Jones NA, Glyn SE, Akiyama S, Hill TD, Hill AJ, Weston SE, Burnett MD, Yamasaki Y, Stephens GJ, Whalley BJ,
Williams CM.Seizure. 2012 Jun;21(5):344-52
Phytocannabinoids as novel therapeutic agents in CNS disorders
Hill AJ, Williams CM, Whalley BJ, Stephens GJ. Pharmacol Ther. 2012 Jan;133(1):79-97
Δ⁹-Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats
Hill AJ, Weston SE, Jones NA, Smith I, Bevan SA, Williamson EM, Stephens GJ, Williams CM, Whalley BJ. Epilepsia.
2010 Aug;51(8):1522-32.
Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo
Jones NA, Hill AJ, Smith I, Bevan SA, Williams CM, Whalley BJ, Stephens GJ. J Pharmacol Exp Ther. 2010
Feb;332(2):569-77.
Cannabinoids: Anti-Seizure Efficacy
Species
Compound
Number of
discrete
conditions/mo
dels/designs
Dose
Anticonvulsan
t
No effect
Proconvulsant
THC
6
31
0.25-200
mg/kg
61%
29%
10%*
CBD
2
21
1-400 mg/kg
81%
19%
0%
Other plant
cannabinoids
2
7
N/A
100%
0%
0%
CB1 receptor
agonists
2
55
N/A
73%
18%
2%
(7% mixed
effect)
Whalley, 2014 American Herbal Pharmacopoeia
Survey of 19 Pediatric Epilepsy
Patients on CBD>THC
• 19 children (2-16 years) used a CBD-enriched
medical marijuana
• 16 (84%) reduction in seizure frequency
– 2 were seizure free
– 8 (42%) >80% reduction in seizures
– 6 had a 25-60% reduction in seizures.
(Porter & Jacobson, Epilepsy & Behavior, 2013)
Survey of 19 Pediatric Epilepsy
Patients on CBD-enriched Cannabis
• Diagnoses: Dravet syndrome (13), Doose
syndrome (4), Lennox Gastaut syndrome (1),
and idiopathic epilepsy (1).
(Porter & Jacobson, Epilepsy & Behavior, 2013)
Medical Uses?
THC is more effective at blocking an enzyme that causes
the brain damage common to Alzheimer's disease than
approved drugs already on the market
low doses of THC inhibit AChE (breaks down
acetylcholine), may thus improve learning and
memory.
The drug also appears to prevent the formation of
neurofibrillary tangles
Eubanks, L.M., et al. (2006) A Molecular Link between the Active Component of
Marijuana and Alzheimer's Disease Pathology, Molecular Pharmaceutics, 3, 773-777.
Medical Uses?
2004 - Israeli soldiers suffering from combat stress
were treated with cannabis to relieve symptoms
– PTSD trials are ongoing
–THC may silence genes that code for vascular
endothelial growth factor (VEGF)
VEGF stimulates the growth of blood vessels in tumors
Does cannabis increase the risk of chronic psychotic illness?
Country
N
Follow up
OR
(95% CI)
Study
Design
Reference
USA
4,494
NA
2.4
Population
based
Tien et al,
1990
Sweden
50,053
25 yrs
2.1
Conscript
Cohort
Andreasson
et al, 1987
Zammit et al,
2002
Netherlands
4,045
2.8
Population
based
Van Os et al,
2002
Population
based
Weiser et al,
2002
1.8
Birthcohort
Fergusson et
al, 2003
3.1
Birthcohort
Arsenault et
al, 2002
2.8
Population
based
Ferdinand et
al 2005
1.7
Population
based
Henquet et al,
2005
1.5
Population
based
Wiles et al,
2006
3 yrs
Israel
9,724
4-15 yrs
New Zealand
(Christchurch)
1,265
New Zealand
(Dunedin)
1,253
Netherlands
1,580
3 yrs
15 yrs
14 yrs
Germany
2,436
4 yrs
United Kingdom
8,580
18 months
2.0
Murray et al 2007. Nature Reviews Neuroscience 8:885-95.
Marinol °: dronabinol
• THC (sintético)
•Aprobado por FDA el 31 de mayo de 1985 para
nauseas y vómitos asociados a quimioterapia en
pacientes con cáncer que no responden
adecuadamente a tratamiento con antieméticos
convencionales
•Aprobado el 22 de diciembre de 1992 para aliviar la
anorexia asociada a la perdida de peso en pacientes
con HIV
•Aprobado en Canadá, Alemania y otros países
•2,5 mg a 10 mg cada 4 horas hasta 40 mg/d
Cesament °:nabilona
•Análogo sintético del THC
•Desarrollado en 1970
•Aprobada por la FDA para NVIQ en 1985
•Comercializado en 2006
Sativex °: Nabiximols
•Extracto vegetal de la planta del cannabis
•FORMA :Sublingual o Spray orobucal
•100microlitros =2.7mg THC y 2.5mg de CBD
(CANNABIDIOL)
•Aprobado en Canadá en 2005
•Aprobado en USA en 2010
•Aprobado en 2011 en UK y España
•Aprobado actualmente en la mayoría de Europa,
Israel, Australia y Nueva Zelanda
Sativex® Characterisation
•Principal Cannabinoids
– THC*
27 mg/ml
– CBD*
25 mg/ml
•Minor Cannabinoids
– CBC*, CBG*, CBN*, THC-V*, CBD-V*, THCA*, CBDA*, CBO#, CBE#,
CBC-V, CBL
•Terpenes
– trans-caryophyllene#, α-caryophyllene#, caryophyllene oxide,
– α-pinene, β-pinene, terpinolene, myrcene, limonene, linalool
– cis-nerolidol, trans-nerolidol, phytol, squalene
•Carotenoids
– β-carotene#
•Fatty Acids
– Linoleic acid, Palmitoleic acid, Linolenic acid, Palmitic acid, Oleic acid, Stearic acid,
Myristic acid, Arachidic acid and Behenic acid
•Sterols
– Β-sitosterol, campesterol, stigmasterol
•Vitamins
– Vitamin E
•Triglycerides
*Items controlled in the BDP specification
– Trilinolenin, Trilinolein…….
#Items
controlled in the BDS specification
Sativex: Esclerosis Múltiple
•Aprobado para el tratamiento de la espasticidad muscular
moderada o severa en la Esclerosis Múltiple luego del uso
de terapia convencional (gabapentin, baclofeno, bzd)
•Dolor neuropatico central en MS en Canadá e Israel
•Dolor crónico relacionado con cáncer
•Dolor neuropatico
Epidiolex (98% CBD) Studies
• NYU enrolled 25 children
and young adults with TRE –
Dravet, LGS, Focal epilepsy,
CDKL4, etc
• 5 other site are enrolling or
will soon enroll 25
children/site (UCSF, Lurie
Children’s, MGH, CHOP,
Great Ormond St)
• Orphan drug indication
approved by FDA for Dravet
and LGS – plans for RCT
Epidiolex : (98%) CBD
Fase 3 en :
Síndrome Gastaut Lennox y Síndrome Dravet
(epilepsias de inicio temprano)
Drogas en estudio
•
HU 308
Manufacturer: Pharmos (licensed from the Hebrew University of
Jerusalem)
Cannabis-Related Properties
Synthetic chemical that specifically binds to the brain's secondary
cannabinoid receptor (CB2).
Suggested Medical Use
Treatment of hypertension; anti-inflammatory.
Approval Status
Not approved for use outside of laboratory research as of Nov. 11,
2013.
Demonstrated efficacy in pre-clinical laboratory studies.
Drogas en estudio
• CT-3 (ajulemic acid)
Manufacturer: Indevus Pharmaceuticals (IDEV on NASDAQ)
Cannabis-Related Properties
Synthetic, more potent analog of THC metabolite THC-11-oic acid.
Suggested Medical Use
Treatment of spasticity and neuropathic pain in MS patients; antiinflammatory properties may help relieve pain from arthritis.
Approval Status
Not approved for use as of Nov. 11, 2013.
Completed Phase I clinical trials as of July 2002.A Phase II study
began in May 2002 in Germany to test its analgesic properties in
patients with neuropathic pain.
Drugs that contain chemicals similar to those in marijuana but
not found in the plant
•
. Dexanabinol
Manufacturer: Solvay Pharmaceuticals (acquired by Abbott Laboratories in 2010;
ABT on NASDAQ)
Cannabis-Related Properties
Synthetic non-psychotropic cannabinoid that blocks NMDA receptors and COX-2
cytokines and chemokines.
Suggested Medical Use
Neuroprotective (protects brain from damage) for use after cardiac surgery;
regain memory and other high-level function following Traumatic Brain Injury
(TBI); possible future use as an anti-cancer drug.
Approval Status
Not approved for use as of Nov. 11, 2013.The Phase III clinical trial involving 846
patients was completed in Dec. 2004; Pharmos said the drug failed to show
statistically significant improvement in the late-stage clinical trial; A Phase I study
to test for the treatment of brain cancer began in Sep. 2012.
Medical Marijuana Laws Get
Tougher
May I prescribe you a joint?
11 states legalized medicinal use with medical
recommendation: AK AZ CA CO HI ME NV OR RI VT WA 35 states allow
use by prescription
BUT
Schedule I substance under the Controlled Substances
Act: high potential for abuse, no currently accepted medical use and a lack of
accepted safety = illegal, except FDA - approved research
programs
so
States with Medical/Recreational Marijuana
(Illegal at Federal Level)
23 Legal Medical Marijuana States and DC
Laws, Fees, and Possession Limits
legalizan el consumo recreativo de
marihuana USA 2014
Colorado
Washington
Oregon
Alaska
Washington D.C.
23 Legal Medical Marijuana States and DC
Laws, Fees, and Possession Limits
•
I. Summary Chart: 23 states and DC have enacted laws to legalize medical marijuana
StateYear PassedHow Passed (Yes Vote)Possession Limit
•
•
•
•
•
1. Alaska1998 Ballot Measure 8 (58%)1 oz usable; 6 plants (3 mature, 3 immature)
2. Arizona 2010 Proposition 203 (50.13%)2.5 oz usable; 0-12 plants
3. California1996 Proposition 215 (56%)8 oz usable; 6 mature or 12 immature plants
4. Colorado2000 Ballot Amendment 20 (54%)2 oz usable; 6 plants (3 mature, 3 immature)
5. Connecticut2012House Bill 5389 (96-51 H, 21-13 S)One-month supply (exact amount to be
determined)
6. DC2010Amendment Act B18-622 (13-0 vote)2 oz dried; limits on other forms to be
determined
7. Delaware2011Senate Bill 17 (27-14 H, 17-4 S)6 oz usable
8. Hawaii2000 Senate Bill 862 (32-18 H; 13-12 S)3 oz usable; 7 plants (3 mature, 4 immature)
9. Illinois2013House Bill 1 (61-57 H; 35-21 S)2.5 ounces of usable cannabis during a period of
14 day
10. Maine1999 Ballot Question 2 (61%)2.5 oz usable; 6 plants
11. Maryland2014House Bill 881 (125-11 H; 44-2 S)30-day supply, amount to be determined
12. Massachusetts2012Ballot Question 3 (63%)60-day supply for personal medical use
13. Michigan2008Proposal 1 (63%)2.5 oz usable; 12 plants
14. Minnesota2014Senate Bill 2470 (46-16 S; 89-40 H)30-day supply of non-smokable
marijuana
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23 Legal Medical Marijuana States and DC
Laws, Fees, and Possession Limits
•
•
•
•
•
•
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15. Montana2004 Initiative 148 (62%)1 oz usable; 4 plants (mature); 12 seedlings
16. Nevada2000 Ballot Question 9 (65%)1 oz usable; 7 plants (3 mature, 4 immature)
17. New Hampshire2013House Bill 573 (284-66 H; 18-6 S)Two ounces of usable
cannabis during a 10-day period
18. New Jersey2010 Senate Bill 119 (48-14 H; 25-13 S)2 oz usable
19. New Mexico2007Senate Bill 523 (36-31 H; 32-3 S)6 oz usable; 16 plants (4 mature, 12
immature)
20. New York2014 Assembly Bill 6357 (117-13 A; 49-10 S)30-day supply non-smokable
marijuana
21. Oregon1998 Ballot Measure 67 (55%)24 oz usable; 24 plants (6 mature, 18 immature)
22. Rhode Island2006 Senate Bill 0710 (52-10 H; 33-1 S)2.5 oz usable; 12 plants
23. Vermont2004 Senate Bill 76 (22-7) HB 645 (82-59)2 oz usable; 9 plants (2 mature, 7
immature)
24. Washington1998 Initiative 692 (59%)24 oz usable; 15 plants
How Many Legal Medical Marijuana Patients Are There in the
United States? 0ct 2014
•
Legal Medical Marijuana Patients:
total medical marijuana users in 19 (out of 23)
states and DC with legal medical marijuana (as
of Oct. 2014)
• Total 1,137,069 personas Average:7.7
(X1000)
Medical Marijuana,
Decriminalization and Legalization
Medical use of marijuana is no longer prosecuted by the
federal government but that use is not recognized by the
FDA.
This means that marijuana is now a:
A. Schedule I substance
B. Schedule II substance
C. Schedule III substance
D. Schedule IV substance
E. Schedule V substance
Dicusion actual
1)Medical Marijuana Law
2)Decriminalization of Marijuana
3)Legalization of Marijuana
4)Impact of Marijuana Use on
Adolescents and Adults
5)Treatment Methodology for
Marijuana Addiction
Federal Controlled Substances Act
Question:
What is a Schedule I drug?
Answer:
1. The drug or other substance has a high potential
for abuse.
2. The drug or other substance has no currently
accepted medical use in treatment in the United
States.
3. There is a lack of accepted safety for use of the
drug or other substance under medical
supervision.
http://www.deadiversion.usdoj.gov/21cfr/21usc/812.htm
Federal Controlled Substances Act
Question:
Why is marijuana a schedule I drug?
Answer:
Under the CSA, marijuana is classified as a
Schedule I drug, which means that the federal
government views marijuana as highly
addictive and having no medical value.
Medical Marijuana Law
Question:
Can a Patient be prescribed marijuana for
medical use?
Answer:
No!
Doctors may not "prescribe" marijuana for
medical use under federal law, though they
can "recommend" its use under the First
Amendment.
Medical Marijuana Law
Question:
What does terminal or debilitating medical condition mean?
Answer:
 Cancer, human immunodeficiency virus (HIV), multiple sclerosis, epilepsy or
other seizure disorder, or spasticity disorders
 Intractable pain, limited for the purpose of this chapter to mean pain
unrelieved by standard medical treatments and medications;
 Glaucoma, either acute or chronic, limited for the purpose of this chapter to
mean increased intraocular pressure unrelieved by standard treatments and
medications
 Crohn's disease with debilitating symptoms unrelieved by standard treatments
or medications
 Hepatitis C with debilitating nausea or intractable pain unrelieved by standard
treatments or medications
 Diseases, including anorexia, which result in nausea, vomiting, wasting,
appetite loss, cramping, seizures, muscle spasms, or spasticity, when these
symptoms are unrelieved by standard treatments or medications
Federal Controlled Substances Act
Question:
What is a schedule II drug?
Answer:
1. The drug or other substance has a high potential for
abuse.
2. 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.
3. Abuse of the drug or other substances may lead to severe
psychological or physical dependence.
http://www.deadiversion.usdoj.gov/21cfr/21usc/812.htm
Federal Controlled Substances Act
Question:
If marijuana is being considered a
medication, will it be moved to Schedule II?
Answer:
The AMA, NORMAL, and various state
attorney generals have petitioned the
congress to do this but to date congress has
denied the petitions. (Clinical Trials!!!)