System in o ccasional and chronic marijuana users Rakesh Awasthi College of Pharmacy Division of Pharmaceutics and Translational Therapetics Research Team Dr Daniel OLeary Professor of ID: 312912
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Slide1
Effect of Acute Marijuana on Cardiovascular Function and Central Nervous
System in o
ccasional
and chronic marijuana users
Rakesh
Awasthi
College of Pharmacy
Division of Pharmaceutics
and
Translational
TherapeticsSlide2Research Team
Dr. Daniel
O'Leary
Professor of Psychiatry, UIHCDr. Laura PontoAssociate Professor in Nuclear Medicine / PET, UIHCDr Maureen D. DonovanProfessor and Chair, Pharmaceutics and Translational Therapeutics, University of Iowa
2Slide3
Health Impact of “Legalized” Marijuana
Impairs
judgement and motor coordinationMost prevalent illicit drug detected in fatally injured drivers.
Relationship between chronic use and ongoing mental illness (schizophrenia)
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Source: http://www.drugabuse.gov/publications/drugfacts/marijuanaSlide4
Frequency of smoking
Occasional Users: smoked
marijuana fewer than 10 times per monthChronic Users: reported smoking 7 or more times weekly for at least the past 2 years.
4Slide5
5
Chronic users reported significantly lower “
highness” ratings, lower heart rates and smaller HR changes, resulting in reduced RPP and RPP changes.Changes in systolic and diastolic blood pressure were
not significantly different
between the
groups (i.e., “chronic use” was
nonsignificant
).
Interesting finding
Ponto et al., Journal
of
Clinical
P
harmacology
2004, 44 (7), 751-66.Slide6
Tolerance
6Slide7
UI Investigation of THC Effects
on Cognition
7
Occasional users:
Low (13.2
mg) and medium
dose (23.5
mg)Chronic users: Medium (24.9
mg) and high
dose (44.9
mg)Slide8
Data Acquired
PK Results
Blood plasma levels of THC and THC-COOH were determined immediately post-smoking (for both placebo and active joint) and at 3 times, at the interval of 15-20 min, within the following 60 min. (4 blood samples/subject/dose)Additional information:Number of puffs, duration of each smoking session, and refined dose for each subject.
PD Measurements (pre-smoking and after each smoking activity)
Heart rate
Blood pressure
Rate pressure product (calculated) - RPP
Subjective effects (highness) – self-reported (scale 1 to 10)
Cerebrovascular function –
rCBF
8Slide9
“Dosing” THC via Marijuana Smoking
Patients were instructed to smoke entire (2.5 in) cigarette using a control inhalation/breath hold/exhalation sequence.
Cigarettes containing THC was smoked for a specific period of time (6-8 min).
The number of puffs were recorded and each was treated as an individual bolus input.
Example
A
cigarette with 44.5 mg (high dose) of THC was smoked in 11 puffs within 7 min of starting time. Then, 11 bolus doses (4.045 mg each) at intervals of 0.0106 h, were used as the THC input.
9Slide10
Optimized
parameters (HDC
)Cl /F(L/h)255.5Vc/F (L)
127.6
k12 (1/h
)
6.34
k21 (1/h
)
0.19
10
Optimizing PK Parameters
Using THC
Profiles for Chronic Users
Using
PKPlus
Module of
GastroPlus
® (44.5
mg Dose)
Rsq
= 0.96Slide11
Summary of PK analysis
The optimized PK parameters can also be used to describe the results obtained from
individual smoking sessions. 11Slide12
OBJECTIVE
Rate
pressure product (RPP) - marker of myocardial oxygen consumptionTo compare the difference in RPP between the two groups (i.e. occasional and chronic users), while taking into account the effect of potential covariates (age, gender, weight, highness etc.).
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