CANNABIS, HIV, & NEUROPSYCHOLOGICAL FUNCTIONING

Transcription

1 CANNABIS, HIV, & NEUROPSYCHOLOGICAL FUNCTIONING Good Medicine? Raul Gonzalez, PhD Associate Professor of Psychology, Psychiatry, & Immunology Director, Substance Use and HIV Neuropsychology (SUHN) Lab

2 The Spread of Legal Marijuana in the United States

3 LOTS OF PEOPLE HAVE TRIED IT. ILLICIT DRUGS 48 Marijuana and Hashish 43 Cocaine 15 Crack 4 Heroin 2 Hallucinogens 15 Inhalants 8 Nonmedical Use of Psychotherapeutics 21 Pain Relievers 14 Tranquilizers 9 Stimulants 8 Methamphetamine 5 Sedatives 3 7.4% used cannabis in the past month % of US Population over 12 [Lifetime Use] NSDUH 2013

4 . INCLUDING PERSONS LIVING WITH HIV 12 27% Recreational use in European samples (Garin et al., 2015) 39% Recreational use in Canadian samples (Harris et al., 2014) 24% Recent use in U.S. sample (4 cities) (Mimiaga et al., 2013) 14 21% Recent use in WIHS sample (D Souza et al., 2012) 72% Ever used in WIHS sample (Kuo et al., 2004)

5 CANNABIS USE DISORDERS ILLICIT DRUGS 2.8 [7.1 million Americans] Marijuana and Hashish 1.8 [4.5 million] Cocaine 0.4 [1 million] Heroin 0.1 Hallucinogens 0.2 Inhalants 0.1 Nonmedical Use of Psychotherapeutics 0.9 Pain Relievers 0.8 Tranquilizers 0.2 Stimulants 0.1 Sedatives 0.1 % of US Population over 12 [Lifetime Use] NSDUH 2010

6 HIV and NP Cannabis and NP HIV, Cannabis, and NP Current Studies

7 HIV & INFECTED T-CELLS ENTER BRAIN Illustration by Lydia Kibiuk. Adapted Lipton, 1994.

8 HIV-ASSOCIATED NEUROCOGNITIVE DISORDERS Antinori et al., 2007; Grant and Sacktor in Gendelman et al., 2012

9 HAD Since CART HAND Since CART Antinori et al., 2007; Grant and Sacktor in Gendelman et al., 2012

10 PATTERN OF DEFICITS IN HIV Primarily reflects prefrontal-striatal abnormalities Motor, psychomotor, processing speed Verbal learning & free recall (spared recognition) Executive Reger et al., 2002

11 HIV NEUROCOGNITIVE IMPAIRMENTS AFFECT DAILY FUNCTIONING Deficits in: Driving ability Marcotte et al., 1999, 2004 Standardized work samples Heaton et al., 1996 Unemployment & vocational functioning Heaton et al., 1996 Activities of daily living Heaton et al., 1995, 1996, 2004 Medication management Albert et al., 1999, Hinkin et al., 2002

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13 CANNABIS AND NEUROCOGNITION 14 Studies N = 1188 Cannabis Users = 704Non-Users = CANNA BIS AND NEURO COGNI TIVE DEFICI TS Simple RT Percp/Motor Attention Executive Motor Verbal Learning Recall/Retrieval Domains Grant, Gonzalez, Carey, Natarajan, & Wolfson, JINS 2003

14 PERSISTING NEUROCOGNITIVE DEFICITS? META-ANALYSES BASED ON 33 STUDIES OF NONINTOXICATED MJ USERS AND SUBSET OF 13 STUDIES WITH MINIMUM 25 DAYS ABSTINENT Effect Size Schreiner & Dunn, 2012

15 PERSISTING NEUROCOGNITIVE DEFICITS? META- ANALYSES BASED ON 33 STUDIES OF NONINTOXICATED MJ USERS AND SUBSET OF 13 STUDIES WITH MINIMUM 25 DAYS ABSTINENT Effect Size Schreiner & Dunn, Experimental and Clinical Psychopharmacology, 2012, 20(5): Schreiner & Dunn, 2012

16 CB1

17 CB1 IS ABUNDANT IN BRAIN Basal Ganglia Hippocampal Formation Amygdaloid Nucleus Cingulate Cortex Cerebellum Herkenham et al., 1990 Egan & Lewis, 2006

18 ENDOCANNABINOIDS

19 ENDOCANNABINOID SYSTEM FUNCTION Modulation of signaling activity Best understood for GABA & Glutamate (Pertwee, 1997) Implicated in various behaviors/functions Feeding, nursing (Fride et al., 2001) Pain regulation (Hohmann & Herkenham, 1999) Addiction (Maldonado, 2006) Immune Functioning (Cabral 2006) Emesis (van Sickle et al., 2001) Neuroprotective Properties (Guzman et al., 2001; Marsicano et al., 2002; Mechoulam 2002) Inhibit release of glutamate Dampens excitotoxic injury Potent antioxidant Reduce damage from experimentally induced ischemia

20 MARIJUANA AS MEDICINE?

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22 MEDICAL BENEFITS Disorder Symptom Evidence Cancer Nausea P. Effective Cancer; HIV Anorexia P. Effective HIV Pain P. Effective Multiple Sclerosis Spasticity P. Effective Pain P. Effective Urinary Dysfunction P. Effective Tremor P. Ineffective Parkinson s Disease Dyskinesia P. Ineffective Huntington s Disease; Tourette Syndrome; Epilepsy unknown Koppel et al., Neurology, 2014 Borgelt et al., Pharmacotherapy, 2013

23 79 Clinical Trials 6,462 Participants 4 studies were judged as low risk for bias Benefits less nausea & vomiting Pain reduction Less spasticity Side Effects Dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, hallucination Whiting et al., 2015

24 Level of Confidence in the Evidence for Adverse Effects of Marijuana on Health and Well-Being. VOLKOW ND ET AL. N ENGL J MED 2014;370:

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26 CURRENT RESEARCH ON HIV & CANNABIS INTERACTIONS Non-human primates Chronic THC administration decreased mortality and associated with less viral load and retention of body mass (Molina et al., 2011) THC administration increased T-cell survival and reduced HIV infection-related inflammation in GI tract of macaques (Molina et al., 2014) No immunological or mortality related differences in THC-treated female macaques, but less weight gain (Molina et al., 2014) Human Subjects Daily marijuana users in WIHS cohort had higher adherence, CD4 count, quality of life, being underweight, and having more mental health & medical comorbidities (D Souza et al., 2012) Lower viral load among daily cannabis users during first year after serconversion (Milloy et al., 2015)

27 STUDIES ON CANNABIS USE & NEUROCOGNITION IN HIV Study Participants Results Abrams et al., (2003) Cristiani, Pukay-Martin, & Bornstein (2004) Chang, Cloak, Yakupov, & Ernst (2006) Byrd et al., (2011) Gonzalez, et al., (2011) N = 62, clinical trial cannabis vs dronabinol, placebo N = 288, stratified by HIV and history of cannabis use N = 96, stratified by HIV and history of cannabis use N = 399 HIV+ substance using individuals N = 86 SDIs, stratified by HIV and hx of cannabis dependence No adverse effects on NP Symptomatic HIV+ frequent cannabis users performed most poorly No additive effects on NP, MRS metabolic abnormalities in basal ganglia and thalamus No difference in HAND prevalence Poorer complex motor skills in those with hx of cannabis dependence

28 CANNABIS AND HIV ON PROCEDURAL MEMORY AND COMPLEX MOTOR SKILLS

29 All currently abstinent polydrug users N = 86 (n = 44) HIV- MJ- (n = 46) HIV+ (n = 42) MJ+ (n = 40) Gonzalez et al, 2011; JCEN

30 HIV+ (n = 47) HIV- (n = 47) MJ+ (n = 42) MJ- (n = 52) seconds to complete seconds to complete MST Blocks MST Blocks seconds on target seconds on target HIV+ (n = 47) HIV- (n = 47) RPT Blocks 6 5 MJ+ (n = 42) MJ- ( n = 52) RPT Blocks

31 MST by Group 140 seconds to complete RF < 1RF 2RF < 0 RF MJ+ AND HIV+ (2RF) MJ+ OR HIV+ (1RF) MJ- AND HIV- (0RF) RPT by Group seconds on target RF < 0 RF 6 5 MJ+ AND HIV+ (2RF) MJ+ OR HIV+ (1RF) MJ- AND HIV- (0RF)

32 OTHER KEY STUDIES Study Participants Results Abrams et al., (2003) N = 62, clinical trial cannabis vs dronabinol, No adverse effects on NP placebo Cristiani, Pukay-Martin, & Bornstein (2004) N = 288, stratified by HIV and history of cannabis use Symptomatic HIV+ frequent cannabis users performed most poorly Chang, Cloak, Yakupov, & Ernst (2006) N = 96, stratified by HIV and history of cannabis use No additive effects on NP, MRS metabolic abnormalities in basal ganglia and thalamus These results indicate that chronic delta-9-thc does not increase viral load or aggravate morbidity and may actually ameliorate SIV disease progression.

33 METHAMPHETAMINE & CANNABIS Gonzalez et al., Meth-/MJ- Meth+/MJ+ Meth+/MJ GDS Exec Attn/WM VF SIP Lrn Rec/Ret Motor

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35 CANNABIS AND NEUROCOGNITION IN HIV

36 PRELIMINARY DATA FROM THE MIND MATTERS PROJECT HIV-/CB- (n = 67) HIV-/CB+ (n = 55) HIV+/CB- (n = 47) HIV+/CB+ (n = 28) Age 35.2 (9.5) 32.0 (8.4) 38.0 (10.1) 37.3 (9.4) HIV-/CB+ < HIV+/CB- % Male 54% 60% 51% 79% ns Years of Education 14.4 (2.2) 13.0 (2.0) 13.6 (2.4) 13.8 (2.3) HIV-/CB- > HIV-/CB+ % African American 54% 64% 70% 64% ns Estimated IQ 97.7 (9.9) 92.1 (12.5) 94.8 (11.9) 96.4 (12.5) HIV-/CB- > HIV-/CB+ Lifetime MDD 15% 13% 9% 21% ns Past Dependence Alcohol 3% 15% 6% 7% ns Cocaine 0% 7% 11% 11% <.01 Cannabis 0% 58% 2% 14% <.001 THCOOH + 0% 96% 0% 82% <.001 CD4 count 608 [395, 774] 583 [346, 704] ns nadir CD4 252 [38, 368] 239 [105, 405] ns HIV viral load (Log10 plasma) 0 [0, 1.7] 0 [0, 1.7] ns % undetectable viral load 72% 61% ns % AIDS Diagnosis 34% 36% ns

37 PRELIMINARY BETWEEN GROUP COMPARISONS ON NP: MIND MATTERS Processing Speed Motor Learning Memory Executive Global HIV-/CB- HIV-/CB+ HIV+/CB- HIV+/CB+

38 REASONS FOR CANNABIS USE Teens (n = 173) Adults: HIV- (n = 12) Adults: HIV+ (n = 15) Get High 94% [25%] 92% [33%] 93% [13%] Have Fun 94% [21%] 92% 93% Socialize 81% 83% 93% [53%] Relax, Reduce Stress 80% [29%] 92% [33%] 80% Feel Happier 61% 83% 60% Feel Less Bored 52% 50% 20% Sleep Better 49% 75% 80% Feel Less Sad 37% 50% 40% Increase Appetite 33% 50% 40% Reduce Pain 29% 58% 53% Reduce Nausea 17% 25% 27% Fit In 8% 8% 12% Reduce Muscle Spasms 4% 42% 20%

39 ACKNOWLEDGEMENTS FIU Gianna Perez Gomez, PhD Brenda Lerner, PsyD, RN Jessica Arguello Ingrid Gonzalez Diana Martinez Melanie Vega Karen Granja Robert Malow, PhD William Pelham, PhD SUHN Lab Team! UIC UCSD Eileen Martin, PhD Jasmin Vassileva, PhD Robin Mermelstein, PhD Randi Schuster Natania Crane Igor Grant, MD Robert Heaton, PhD Susan Tapert, PhD SUBSTANCE USE AND HIV NEUROPSYCHOLOGY

40 Ongoing FIU