Allogeneic HUman Mesenchymal Stem Cell InfusioN Versus Placebo in Subjects With Alcohol Use Disorder and Major DepreSsion.

Eighty (80) subjects fulfilling all inclusion/exclusion criteria's will be randomly assigned
to receive allogeneic hMSCs or placebo in a 1:1 blinded fashion.

Forty (40) subjects will be treated with a single administration of allogeneic hMSCs: 100 x
10^6 (100 million) allo-hMSCs of cells delivered via a single peripheral intravenous
infusion.

Forty (40) subjects will be treated with a placebo administration consisting of 1% human
albumin serum in Plasma-Lyte A delivered via a single peripheral intravenous infusion.

The Allo-hMSCs will be supplied from an allogeneic human mesenchymal stem cell source or
commercial grade bone marrow product and will be manufactured by the University of Miami.

The study will last approximately 14 months with six follow-up visits, which will occur every
2 weeks at 2, 4, 6, 8, 10, and 12 weeks following treatment infusion and then at 6, 9 and 12
months.

Inclusion Criteria:

1. Provide written informed consent.

2. Subjects age >18 and <75 years at the time of signing the Informed Consent Form.

3. Diagnostic and Statistical Manual of Mental Disorder-5 criteria for Alcohol Urge
Questionnaire (moderate or severe defined as meeting 4 or more of the 11 criteria) AND
a concurrent Diagnostic and Statistical Manual of Mental Disorder-5 recurrent unipolar
major depression with HRSD-25 score of 18 or above.

4. A history of a depressive episode occurring or persisting during a period of one-month
abstinence.

5. Participants should express the desire to reduce or stop alcohol consumption, report
28 or more standard drinks (SD) per week for males or 21 for females over four weeks
during the 90 days preceding study enrollment.

6. Increased inflammation ([serum C-reactive protein] ≥3.0 mg/L.

7. Agree to taper and discontinue antidepressant medications during the 12-week trial.

8. Able to provide informed consent and comply with study procedures.

9. Able to read English and understand study instruments.

10. Entry criteria for depression and alcohol use disorder (moderate or severe) will be
established using the Structured Clinical Interview for Diagnostic and Statistical
Manual of Mental Disorders (SCID) for categorical diagnosis.

11. Have a score of ≥18 on the Hamilton Depression Rating Scale for Depression (HAM-D).

Exclusion Criteria:

1. Acute suicidality.

2. Any lifetime history of bipolar disorder, schizophrenia, or schizoaffective disorder.

3. Active psychotic disorder, eating disorder, or substance use disorder except for
alcohol and tobacco or "mild" cannabis use disorder within 6 months of enrollment.

4. Any lifetime history of autoimmune or immunodeficiency syndrome.

5. Treatment with any psychotropic (including hypnotic), steroidal, or anti-inflammatory
medication (including NSAIDs) within 2 weeks of treatment randomization (6 weeks for
fluoxetine).

6. Any current use of medication that affect alcohol consumption such as acamprosate,
disulfiram, naltrexone (po or IM), topiramate, or sedative-hypnotics including
benzodiazepines or any psychostimulant.

7. Being enrolled in an alcohol treatment program (self-help groups participation such as
Alcoholics Anonymous or Dual Diagnosis self-help are allowed).

8. Active medical condition that could cause or exacerbate depressive symptoms (e.g.,
hypothyroidism, anemia).

9. Currently pregnant or breast-feeding.

10. Lack of use of a reliable means of contraception methods. (Female subjects of
childbearing potential must undergo a serum or urine pregnancy test at screening and
within 36 hours prior to infusion.)

11. First major depressive episode after 50 years of age.

12. Any evidence of current infection including serum positive for HIV, hepatitis BsAg or
Viremic hepatitis.

13. Medical conditions with known autoimmune or inflammatory mechanisms including any
chronic allergic condition.

14. Positive urine screens for any drug of abuse other than cannabis at baseline.

15. Inability to read or understand study forms or informed consent or the presence of any
other conditions or factors, which in the opinion of the investigator would make the
patient unsuitable for study participation.

16. Prior history of a suicide attempt, within the past year.

17. Have hypersensitivity to dimethyl sulfoxide (DMSO).

18. Have a clinical history of malignancy within 3 years (i.e., subjects with prior
malignancy must be disease free for 3 years), except curatively-treated basal cell
carcinoma, squamous cell carcinoma, melanoma in situ or cervical carcinoma.

19. Be serum positive for HIV, hepatitis BsAg or Viremic hepatitis C.

20. Be currently participating (or participated within the previous 30 days) in an
investigational therapeutic or device trial.