Table 1.
Summary of the included studies divided according to the experimental conditions.
| Author & Year | Study Description | Species, Model (Anaesthetic & Route) | Sample Size | THC Dose | THC Route | Time of THC Administration | Time of Haemodynamic Measurements | Basal Parameters * | Outcomes and Comments |
|---|---|---|---|---|---|---|---|---|---|
| Anaesthetised animals | |||||||||
| Cavero 1972 [25] | Investigate the haemodynamic effects of THC | Dogs Anaesthetised (pentobarbital, iv) | 11 | 2.5 mg/kg | i.v. | Post-anaesthesia | Continues for 30 m post-drug | - | THC altered distribution of regional BF, and reduced HR and BP. |
| Cavero 1973a [26] | Investigate the haemodynamic effects of THC | Dogs Anaesthetised (pentobarbital, iv) | 23 | 39 µg/kg–2.5 mg/kg | i.v. | Post-anaesthesia | Continues for 2 h post-drug | C: HR:169, BP:91.7; T: HR:165.7, BP:93.5 | THC caused reduction in HR and BP mediated via central nervous system. |
| Cavero 1973b [27] | Characterise the mechanism of action of THC on HR | Dogs Anaesthetised (pentobarbital, iv) | 29 | 39 µg/kg–5 mg/kg | i.v. | Post-anaesthesia | Continues for 140 m post-drug | - | THC induced reduction in HR through alteration of autonomic innervation to myocardium. |
| Cavero 1974 [19] | Investigate the effect of THC on venous return | Dogs (heart bypass) Anaesthetised (dibucaine, spinal) | 8 | 2.5 mg/kg | i.v. | Post-anaesthesia | Pre-drug and continues for 30 m post-drug | C: HR:156, BP:85.8; T: HR:147, BP:85. | THC caused reduction in HR and BP, and reduced venous return. |
| Daskalopoulos 1975 [28] | Investigate the mechanism of THC on CV system | Cats Anaesthetised (urethane, iv) | 40 | 30–300 µg/kg | i.v. | Post-anaesthesia | 20 m post-drug | - | THC reduced HR and BP mediated via central nervous system. |
| Adams 1976 [29] | Examined the CV effects of THC | Rats Anaesthetised (urethane, ip) | 72 | 0.1–3 mg/kg | i.v. | Post-anaesthesia | Continues for 30 min post-drug | C: HR:316.2, BP:76.2; T: HR:314.8, BP:73.5. | THC caused reduction in HR and biphasic BP response (↑ BP followed by ↓ BP), suggesting that THC depressed CV reflex functions. |
| Jandhyala 1976 [30] | Evaluated possible interaction with THC on HR | Dogs Anaesthetised (pentobarbital) | 12 | 1 mg/kg | s.c. | Twice/day for 7 days Pre-anaesthesia | On the 7th day post-anaesthesia | - | Chronic THC antagonised the elevation in HR induced by the anaesthetic agent via vagal stimulation. |
| Jandhyala 1977 [31] | Determined chronic administration of THC on CV function | Dogs Anaesthetised (pentobarbital) | 16 | 1 mg/kg | s.c. | Twice/day for 7 days Pre-anaesthesia | On the 7th day post-anaesthesia | - | Chronic THC had no effect on haemodynamics. |
| Jandhyala 1978 [32] | Investigated prolonged THC effects on CV system | Dogs Anaesthetised (pentobarbital) | 16 | 2 mg/kg | s.c. | Single dose per day for 35 days | On the 35th day post-anaesthesia | - | Chronic THC increased BF in femoral and mesenteric arteries with no effect on HR or BP. |
| McConnell 1978 [33] | Examined the effects of THC on salivary flow | Cats Anaesthetised (urethane & pentobarbital, ip) | 20 | 0.1–2 mg/kg | i.v. | Post-anaesthesia | Continues for 1 h post-drug | - | THC had no effect in stimulated salivary flow of cats. THC caused a reduction in HR and BP. |
| Siqueira 1979 [24] | Clarify the triple BP response post-THC | Rats Anaesthetised (urethane, ip) | 50 | 1–10 mg/kg | i.v. | Post-anaesthesia | Continues for 70 m post-drug | - | THC induced triphasic BP response (↓ BP via vagal stimulation, then ↑ BP not dependent on sympathetic activity followed by ↓ BP due to central decrease in sympathetic tone). |
| Kawasaki 1980 [23] | Investigated the effect of THC on the CV system and behavior changes | Rats Anaesthetised (urethane, ip) | 29 | 1–5 mg/kg | i.v. | Post-anaesthesia | Continues for 70 m post-drug | - | THC induced CV effects (↓ HR and ↑ BP) through vagal activity, and influence behavior changes to brain stimulation. |
| Schmeling 1981 [34] | Investigated the effect of THC on hypothalamus | Cats Anaesthetised (urethane, ip) | 12 | 2 mg/kg | i.v. | Post-anaesthesia | Continues for 30 m post-drug | - | THC produced significant reductions in HR and BP and attenuated the pressor response threshold suggesting that THC reduces sympathetic activity. |
| Estrada 1987 [35] | Investigated the CV effects of THC | Rats Anaesthetised (pentobarbital, ip) | 28 | 0.078–5 mg/kg | i.v. | Post-anaesthesia | 3-12 min post-drug | - | THC produced adverse effects on the CV system (↓ HR and ↓ BP) |
| Krowicki 1999 [36] | Investigated whether CB1 activation by THC inhibits gastric motor function | Rats Anaesthetised (ketamine and xylazine) | 36 | 0.02–2 mg/kg | i.v. | Post-anaesthesia | Continues for 10 m post-drug | - | THC decreased gastric motor function, HR, and BP via autonomic effects mediated by CB1. |
| Conscious animals | |||||||||
| Kaymakcalan 1974 [37] | Investigated chronic effects of THC on HR | Rats Conscious | 20 | 10 mg/kg | s.c. | Single dose per day for 16 days | Hourly interval to 6 h on the 1st, 4th, 8th and 16th days | - | THC produced marked reduction in HR |
| Borgen 1974 [38] | Examined possible interaction of CBD on THC effects | Rabbits Conscious | 8 | 3 mg/kg | i.v. | Pre-test | Pre-drug and hourly interval to 7 h post-drug | C: HR:264; T: HR:276 | CBD reduced the hypothermic effect of THC and attenuated the depressant effects of THC on respiration, rectal temperature and HR |
| Brown 1974 [20] | Investigated CV response to THC | Bats Conscious | 12 | 100 and 200 mg/kg | i.p. | Pre-test | Pre-drug and continues for 145 m post-drug | C: HR:436, BP:101; T: HR:390, BP:114 | THC induced hypothermia and reduction in HR and BP. |
| Osgood 1977 [22] | Investigated THC effects on HR | Rats Conscious | 18 | 0.5 mg/kg | i.p. | Pre-test | Continues for 30 m post-drug | - | THC had minimal effect on BP and caused an increase in HR, which may be related to central mediation release of epinephrine from adrenal gland. |
| Kawasaki 1980 [23] | Investigated the effects of THC on the CV system and behavior changes | Rats Conscious | 21 | 4–8 mg/kg | i.p. | Pre-test | Continues for 2 h post-drug | - | THC induced CV effects (↓ HR and ↑ BP) through vagal activity, and influenced behavior changes to brain stimulation. |
| Matsuzaki 1987 [39] | Examined the effects of THC on EEG, body temperature, and HR | Monkeys Conscious | 6 | 0.4–4 mg/kg | i.p. | Pre-test | Continues for 5 h post-drug | - | THC induced reduction in HR and hypothermia and induced responses of EGG along with behavioral depression and alertness. |
| Hayakawa 2007a [40] | Investigated CBD and THC effects on ischemic brain damage | Stroke Mice Conscious | 17 | 10 mg/kg | i.p. | Pre-, 3 and 4 h post-occlusion, and 1 and 2 h post-reperfusion | BP and HR: pre-reperfusion. CBF: continued 4 h post-occlusion and 1 post-reperfusion | - | Pre and post-ischemic treatment with CBD induced neuroprotection, whereas only preischemic treatment with THC induced neuroprotection. THC increased CBF with no effects on BP or HR |
| Hayakawa 2007b [41] | Explored the development of tolerance of THC and CBD neuroprotection | Stroke Mice Conscious | 7 | 10 mg/kg | i.p. | Pre-occlusion and 3 h post-occlusion. Single dose per day for 14 days | During 4 h and on day 14 post-occlusion | - | Repeated treatment with CBD, but not THC, induced neuroprotection with development of tolerance. THC increased CBF on day 1 only with no effects on BP or HR. |
| Stress and hypertensive animal models | |||||||||
| Williams 1973 [42] | Studied the effects of THC on BP | Rats Stress | 30 | 20 mg/kg | s.c. | Single dose per day for 4 days | Pre-drug, 4 h, 48 and 96 h post-drug | C: BP:128; T: BP:129 | THC reduced BP |
| Birmingham 1973 [43] | Studies the effects of THC on BP | Rats Hypertensive | 10 | 3 mg/kg | i.p. | Single dose per day for 7 days | Hourly to 5 h for 7 days | - | THC reduced BP |
| Kosersky 1978 [44] | Examined the antihypertensive effects of THC | Rats Hypertensive | 12 | 25 mg/kg | Oral | Single dose per day for 10 days | 4 h and every day for 14 days post-drug | - | THC effectively reduced BP to the same degree over the treatment period. |
| Humans | |||||||||
| Karniol 1973 [45] | Compared the effects of 8-THC and 9-THC | Human Healthy | 21 | 5–20 mg | Inhale | Pre-test | Avrg. of 20 m post-drug | C: HR:82; T: HR:85 | 9-THC was twice as active as 8-THC in increasing HR and caused more subjective symptoms. |
| Karniol 1975 [46] | Examined the interaction between THC and CBN | Human Healthy | 5 (M) | 25 mg | Oral | Pre-test | 50, 70 and 160 m post-drug | - | THC induced increase in HR and psychological effects. No change on THC effects when combined with CBN |
| Zimmer 1976 [47] | Examined changes of somatic parameters post-THC | Human Healthy | 36 | 250 µg/kg | Oral | Pre-test | Pre-drug and 4 h post-drug | C: HR:87.9, BP:127.5; T: HR:89, BP:123 | THC raised HR with no changes on other parameters including BP |
| Haney 2007 [48] | Determined the effects of naltrexone in combination with THC | Human Healthy | 21 (11 M & 10 F) | 2.5–10 mg | Oral | Pre-test | Continues for 6 h post-drug | - | Naltrexone enhanced intoxication effects of THC; THC increased HR |
| Beaumont 2009 [21] | Evaluated whether THC has inhibitory effect on transient esophageal sphincter | Human Healthy | 18 (M) | 10 and 20 mg | Oral | Pre-test | Continues for 4 h post-drug | C: HR:59; T: HR:59 | THC inhibited the increased induced meal transient esophageal sphincter relaxation. THC increased HR and decreased BP |
| Klooker 2011 [49] | Assessed the effect of THC on rectal sensation | Human Healthy and IBD | 10 and 12 | 5 and 10 mg | Oral | Pre-test | Continues for 105 m post-drug | - | THC had no effect on rectal perception to distension. THC increased HR with no effect on BP |
Abbreviations: BP: blood pressure, BF: Blood flow, C: control group, CB1: cannabinoid receptor 1, CBD: Cannabidiol, CBF: cerebral blood flow, CBN: cannabinol, CV: cardiovascular, D: THC treated group, F: females, G: gender, h: hour(s), HR: heart rate, , IBD: inflammatory bowel disease i.p.: intraperitoneal, i.v.: intravenous, M: males, m: minute(s), s.c.: Subcutaneous, T: treatment group, THC: ∆9-Tetrahydrocannabinol. ↑: increased, ↓: decreased. * Basal parameters values before intervention (i.e., anaesthetic agents or THC). The units of the parameters are HR: beats/m, BP: mmHg, BF: mL/m.