E-cigarette / Vapor Inhalation

So called "vaping" procedures break down into two categories at present. One method heats the marijuana to a high temperature below the combustion threshold and collects cannabinoid-infused air into a balloon (Volcano® type devices). A second method uses e-cigarette technology which we have adapted for our research program. The picture to the right illustrates a standard rat cage fitted with a sealed lid. This permits the controlled airflow through the chamber and the incorporation of vapor from an e-cigarette cartridge upon demand.

Additional reading can be found in the tlneuro blog Vape inhalation archive.

Cannabinoids

A primary focus of our work is on the primary active constituent of marijuana ( Δ9-tetrahydrocannabinol; THC). It appears that growing numbers of cannabis consumers are using non-combustible techniques, based on the evidence of a plethora of Web sites advertising methods, an emerging literature showing human practices (Giroud et al, 2015, Morean et al, 2015) and from suggestions that e-cigarette delivery may offer a safer alternative for medical cannabis consumers (Varlet et al, 2016). Our first paper (Nguyen et al., 2016a) demonstrated that vapor inhalation of THC reduces body temperature, decreases locomotor activity and attenuates detection of a noxious stimulus. These are three of the four traditional behavioral measures of cannabinoid activity in a rodent and thus verify the efficacy of this approach. We next showed in further studies that male and female rats exhibited approximately the same acute effects (Javadi-Paydar et al., 2018) and that tolerance develops with twice-daily exposure for four days (Nguyen et al., 2018).

We are also interested in the effects of cannabidiol (CBD) a constituent of marijuana that does not produce the strong psychotropic effects associated with THC. Our studies seek primarily to determine how CBD may modulate the effects of THC when the two are ingested together. We have found, at least in the rat models, that CBD enhances the effects of THC (Javadi-Paydar et al., 2018). One interesting thing that has emerged is that CBD inhalation reduces the body temperature of rats while this is not observed when CBD is injected. This is a case where the route of administration produces qualitatively different drug effects and will require some additional follow up work.

Psychostimulants

One of the primary interests of the laboratory is the use and abuse of psychostimulants including methamphetamine, MDMA and substituted cathinone stimulants. Inhaled use of methamphetamine is more common than other routes of administration in habitual and dependent users. Furthermore, the SAMHSA/TEDS treatment admission database for 2012 shows 4.7% of treatment seekers in the USA were admitted for smoked cocaine vs 2.2% for other routes of cocaine administration as the primary reason for treatment. Despite this, preclinical models which incorporate inhaled exposure to psychomotor stimulants are not commonly available. E-cigarette technology has further facilitated inhalation of methamphetamine (Evans 2014; Rass et al. 2015), “bath salts” (Johnson and Johnson 2014; Rass et al. 2015) and “flakka” (α-pyrrolidinopentiophenone; alpha-PVP) as reported (Anderson 2015) in one case of paranoid public behavior. Additional evidence exists in popular drug-user forums such as www.bluelight.org host sub-threads for the discussion of administering several different stimulants in e-cigarettes. We have thus been working to determine if active doses of psychostimulants can be delivered to rats using this technology. Our first publication (Nguyen et al., 2016b) showed that methamphetamine, mephedrone and MDPV increase locomotor activity when delivered with the e-vape model.

Nicotine

The primary use of e-cigarettes is for the delivery of nicotine. While nicotine addiction is not a primary focus of the laboratory, we are interested in the intersection of nicotine and THC. A substantial population of cannabis users consume it via "blunts" which are cigars hollowed out and filled with cannabis. Other individuals may ingest nicotine and THC in a sequential manner. Thus, we are developing some studies to determine how nicotine inhalation can be modeled in the rat. In our first paper, Javadi-Paydar et al. 2019a (Drug Alcohol Depend) we find that the effects of nicotine and THC are probably independent when co-inhaled in the same vapor exposure session. We then showed similarly independent effects occur with the co-inhlation of CBD and nicotine in Javadi-Paydar et al., 2019b ( Pharmacol Biochem Behav).

Vape Publications

Nguyen, J.D., Creehan, K.M., Kerr, T.M. and Taffe, M.A. Lasting effects of repeated Δ9-tetrahydrocannabinol (THC) vapor inhalation during adolescence in male and female rats. Brit J Pharmacol, 2019, in press. [ Publisher Site ][ PubMed ]

Javadi-Paydar, M., Creehan, K.M., Kerr, T.M. and Taffe, M.A. Vapor inhalation of cannabidiol (CBD) in rats. Pharmacol Biochem Behav, 2019 Jul 20:172741. doi: 10.1016/j.pbb.2019.172741. [ Publisher Site ][ PubMed ]

Nguyen, J.D., Grant, Y., Creehan, K.M., Hwang, C.S., Vandewater, S.A., Janda, K.D., Cole, M. and Taffe, M.A. Δ9-tetrahydrocannabinol Attenuates Oxycodone Self-Administration Under Extended Access Conditions, 2019, Neuropharmacology, 151:127-135. [ Publisher Site ][ PubMed ]

Javadi-Paydar, M., Kerr, T.M., Harvey, E.L., Cole, M., and Taffe, M.A. Effects of Nicotine and THC Vapor Inhalation Administered By An Electronic Nicotine Delivery System (ENDS) In Male Rats. Drug Alcohol Depend, 2019 May, 198:54-62. [ Publisher Site ]

Nguyen, J.D., Grant, Y., Kerr, T.M., Gutierrez, A., Cole, M., and Taffe, M.A. Tolerance to the Hypothermic and Antinoceptive effects of Δ9-tetrahydrocannabinol (THC) Vapor Inhalation In Rats. Pharmacol Biochem Behav, 2018 Sept, 172:33-38. [ Publisher Site ][ PubMed ]

Javadi-Paydar, M., Nguyen, J.D., Kerr, T.M., Grant, Y., Vandewater, S.A., Cole, M., and Taffe, M.A. Effects Of Δ9-THC And Cannabidiol Vapor Inhalation In Male And Female Rats. Psychopharmacology, 2018 Jun 16, 235:2541-2557. [ Publisher Link ][ Free Viewable Link ][ PubMed ]

Vendruscolo, J.C.M., Tunstall, B.J., Carmack, S.A., Schmeichel, B.E., Lowery-Gionta, E.G., Cole, M., George, O., Vandewater, S.A., Taffe, M.A., Koob, G.F. and Vendruscolo, L.F. Compulsive-like sufentanil vapor self-administration in the rat, Neuropsychopharmacology, 2018, 43:801-809.

Nguyen, J.D., Bremer, P.T., Hwang, C.S., Vandewater, S.A., Collins, K.C., Creehan, K.M., Janda, K.D. and Taffe, M.A. Effective active vaccination against methamphetamine in female rats, Drug Alcohol Depend, 2017, 175:179-186. [ Publisher Site ][ PubMed ]

Nguyen, J.D., Aarde, S.M., Cole, M., Vandewater, S.A., Grant, Y. and Taffe, M.A. Locomotor stimulant and rewarding effects of inhaling methamphetamine, MDPV and mephedrone via electronic cigarette-type technology, Neuropsychopharmacology, 2016b, 41:2759-2771. [ Publisher Site ][ PubMed]

Nguyen, J.D., Aarde, S.M., Vandewater, S.A., Grant, Y., Stouffer, D.G., Parsons, L.H., Cole, M. and Taffe, M.A. Inhaled delivery of Δ9-tetrahydrocannabinol (THC) to rats by e-cigarette vapor technology, Neuropharmacology, 2016a, 109:112-120. [ Publisher Site ][ PubMed ]

Vapor inhalation research in the Taffe Laboratory was supported by subcontract of USPHS Grant R44 DA041967 awarded to La Jolla Alcohol Research, Inc. We continue to collaborate with the company on an ad hoc basis.